Tissues and Tumor Microenvironment (TME) in 3D: Models to Shed Light on Immunosuppression in Cancer
Abstract
:1. Introduction
2. Mechanisms of Cancer Immunosuppression
3. Tumor-Driven Mechanisms of Cancer Immunosuppression
3.1. TP53
3.2. NF-κB
3.3. Wnt Signaling
3.4. PTEN
3.5. MYC
3.6. RAS
3.7. Moving Forward
4. Overview of Current Experimental Models in Cancer
4.1. Mouse Models
4.1.1. Syngeneic Mouse Models
4.1.2. Humanized Mouse Models
4.2. 3D Models and Co-Cultures—Engineering Complexity to Mirror Physiology
4.2.1. Spheroids
4.2.2. Organoids
5. Future Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Ribas, J.; Wolchok, D. Cancer immunotherapy using checkpoint blockade. Science 2018, 359, 1350. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Guedan, S.; Ruella, M.; June, C.H. Emerging Cellular Therapies for Cancer. Annu. Rev. Immunol. 2019, 37, 145–171. [Google Scholar] [CrossRef] [PubMed]
- Sanmamed, M.F.; Chen, L. A Paradigm Shift in Cancer Immunotherapy: From Enhancement to Normalization. Cell 2018, 175, 313. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wellenstein, M.D.; de Visser, K.E. Cancer-Cell-Intrinsic Mechanisms Shaping the Tumor Immune Landscape. Immunity 2018, 48, 399. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Murciano-Goroff, Y.R.; Warner, A.B.; Wolchok, J.D. The future of cancer immunotherapy: Microenvironment-targeting combinations. Cell Res. 2020, 30, 507–519. [Google Scholar] [CrossRef] [PubMed]
- Binnewies, M.; Roberts, E.W.; Kersten, K.; Chan, V.; Fearon, D.F.; Merad, M.; Coussens, L.M.; Gabrilovich, D.I.; Ostrand-Rosenberg, S.; Hedrick, C.C.; et al. Understanding the tumor immune microenvironment (TIME) for effective therapy. Nat. Med. 2018, 24, 541–550. [Google Scholar] [CrossRef]
- Togashi, Y.; Shitara, K.; Nishikawa, H. Regulatory T cells in cancer immunosuppression—Implications for anticancer therapy. Nat. Rev. Clin. Oncol. 2019, 16, 356–371. [Google Scholar] [CrossRef]
- Esfahani, K.; Roudaia, L.; Buhlaiga, N.; Del Rincon, S.; Papneja, N.; Miller, W. A Review of Cancer Immunotherapy: From the Past, to the Present, to the Future. Curr. Oncol. 2020, 27, 87–97. [Google Scholar] [CrossRef]
- Zappasodi, R.; Wolchok, J.D.; Merghoub, T. Strategies for Predicting Response to Checkpoint Inhibitors. Curr. Hematol. Malig. Rep. 2018, 13, 383. [Google Scholar] [CrossRef]
- Otsuka, Y.; Nishikori, M.; Arima, H.; Izumi, K.; Kitawaki, T.; Hishizawa, M.; Takaori-Kondo, A. EZH2 inhibitors restore epigenetically silenced CD58 expression in B-cell lymphomas. Mol. Immunol. 2020, 119, 35–45. [Google Scholar] [CrossRef]
- Amanda, J.; Oliver, A.S.D.; Simon, P.K.; Sherly, M.; Jack, D.C.; von Scheidt, B.; Beavis, P.A.; House, I.G.; Van Audernaerde, J.R.M.; Darcy, P.K.; et al. Tissue-specific tumor microenvironments influence responses to immunotherapies. Clin. Transl. Immunol. 2019, 8, e1094. [Google Scholar]
- Duan, Q.; Zhang, H.; Zheng, J.; Zhang, L. Turning Cold into Hot: Firing up the Tumor Microenvironment. Trends Cancer 2020, 6, 605–618. [Google Scholar] [CrossRef]
- Gholami, M.D.; Kardar, G.A.; Saeedi, Y.; Heydari, S.; Garssen, J.; Falak, R. Exhaustion of T lymphocytes in the tumor microenvironment: Significance and effective mechanisms. Cell. Immunol. 2017, 322, 1–14. [Google Scholar] [CrossRef]
- Xia, A.; Zhang, Y.; Xu, J.; Yin, T.; Lu, X.-J. T Cell Dysfunction in Cancer Immunity and Immunotherapy. Front. Immunol. 2019, 10, 1719. [Google Scholar] [CrossRef] [Green Version]
- Haslam, A.; Prasad, V. Estimation of the Percentage of US Patients with Cancer Who Are Eligible for and Respond to Check-point Inhibitor Immunotherapy Drugs. JAMA Netw. Open 2019, 2, e192535. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Nixon, N.A.; Blais, N.; Ernst, S.; Kollmannsberger, C.; Bebb, G.; Butler, M.; Smylie, M.; Verma, S. Current Landscape of Immunotherapy in the Treatment of Solid Tumours, with Future Opportunities and Challenges. Curr. Oncol. 2018, 25, 373–384. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pardoll, D.M. The blockade of immune checkpoints in cancer immunotherapy. Nat. Rev. Cancer 2012, 12, 252–264. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dovedi, S.J.; Adlard, A.L.; Lipowska-Bhalla, G.; McKenna, C.; Jones, S.; Cheadle, E.J.; Stratford, I.J.; Poon, E.; Morrow, M.; Stewart, R.; et al. Acquired Resistance to Fractionated Radiotherapy Can Be Overcome by Concurrent PD-L1 Blockade. Cancer Res. 2014, 74, 5458–5468. [Google Scholar] [CrossRef] [Green Version]
- Gabrilovich, D.I.; Nagaraj, S. Myeloid-derived suppressor cells as regulators of the immune system. Nat. Rev. Immunol. 2009, 9, 162–174. [Google Scholar] [CrossRef] [PubMed]
- Fleming, V.; Hu, X.; Weber, R.; Nagibin, V.; Groth, C.; Altevogt, P.; Utikal, J.; Umansky, V. Targeting Myeloid-Derived Suppressor Cells to Bypass Tumor-Induced Immunosuppression. Front. Immunol. 2018, 9, 398. [Google Scholar] [CrossRef]
- Bai, R.; Chen, N.; Li, L.; Du, N.; Bai, L.; Lv, Z.; Tian, H.; Cui, J. Mechanisms of Cancer Resistance to Immunotherapy. Front. Oncol. 2020, 10, 1290. [Google Scholar] [CrossRef]
- Terabe, M.; Park, J.M.; Berzofsky, J.A. Role of IL-13 in regulation of anti-tumor immunity and tumor growth. Cancer Immunol. Immunother. 2004, 53, 79–85. [Google Scholar] [CrossRef]
- Martin, M.; Wei, H.; Lu, T. Targeting microenvironment in cancer therapeutics. Oncotarget 2016, 7, 52575. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Vinay, D.S.; Ryan, E.P.; Pawelec, G.; Talib, W.H.; Stagg, J.; Elkord, E.; Lichtor, T.; Decker, W.K.; Whelan, R.L.; Kumara, H.M.C.S.; et al. Immune evasion in cancer: Mechanistic basis and therapeutic strategies. Semin. Cancer Biol. 2015, 35, S185–S198. [Google Scholar] [CrossRef] [PubMed]
- Katoh, H.; Wang, D.; Daikoku, T.; Sun, H.; Dey, S.K.; Dubois, R.N. CXCR2-expressing myeloid-derived suppressorcells are essential to promote colitis-associated tumorigenesis. Cancer Cell 2013, 24, 631–644. [Google Scholar] [CrossRef] [Green Version]
- Feig, C.; Jones, J.O.; Kraman, M.; Wells, R.J.B.; Deonarine, A.; Chan, D.S.; Connell, C.M.; Roberts, E.W.; Zhao, Q.; Caballero, O.L.; et al. Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immuno-therapy in pancreatic cancer. Proc. Natl. Acad. Sci. USA 2013, 110, 20212–20217. [Google Scholar] [CrossRef] [Green Version]
- Biasci, D.; Smoragiewicz, M.; Connell, C.M.; Wang, Z.; Gao, Y.; Thaventhiran, J.E.D.; Basu, B.; Magiera, L.; Johnson, T.I.; Bax, L.; et al. CXCR4 inhibition in human pancreatic and colorectal cancers induces an integrated immune response. Proc. Natl. Acad. Sci. USA 2020, 117, 28960–28970. [Google Scholar] [CrossRef]
- Nakamura, K.; Kassem, S.; Cleynen, A.; Chrétien, M.-L.; Guillerey, C.; Putz, E.M.; Bald, T.; Förster, I.; Vuckovic, S.; Hill, G.R.; et al. Dysregulated IL-18 Is a Key Driver of Immunosuppression and a Possible Therapeutic Target in the Multiple Myeloma Microenvironment. Cancer Cell 2018, 33, 634–648.e5. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, X.; Lin, Y. Tumor necrosis factor and cancer, buddies or foes. Acta Pharmacol. Sin. 2008, 29, 1275–1288. [Google Scholar] [CrossRef] [Green Version]
- Teijeira, A.; Garasa, S.; Gato, M.; Alfaro, C.; Migueliz, I.; Cirella, A.; Melero, I. CXCR1 and CXCR2 Chemokine Receptor Agonists Produced by Tumors Induce Neutrophil Extracellular Traps that Interfere with Immune Cytotoxicity. Immunity 2020, 52, 856–871. [Google Scholar] [CrossRef] [PubMed]
- Dowling, M.R.; Kan, A.; Heinzel, S.; Marchingo, J.M.; Hodgkin, P.D.; Hawkins, E.D. Regulatory T Cells Suppress Effector T Cell Proliferation by Limiting Division Destiny. Front. Immunol. 2018, 9, 2461. [Google Scholar] [CrossRef] [PubMed]
- Collison, L.W.; Workman, C.J.; Kuo, T.T.; Boyd, K.; Wang, Y.; Vignali, K.M.; Cross, R.; Sehy, D.; Blumberg, R.S.; Vignali, D.A.A. The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature 2007, 450, 566–569. [Google Scholar] [CrossRef]
- Blagih, J.; Buck, M.D.; Vousden, K.H. p53, cancer and the immune response. J. Cell Sci. 2020, 133, jcs237453. [Google Scholar] [CrossRef] [Green Version]
- Stein, Y.; Aloni-Grinstein, R.; Rotter, V. Mutant p53-a potential player in shaping the tumor-stroma crosstalk. J. Mol. Cell Biol. 2019, 11, 600–604. [Google Scholar] [CrossRef] [PubMed]
- Guo, G.; Cui, Y. New perspective on targeting the tumor suppressor p53 pathway in the tumor microenvironment to en-hance the efficacy of immunotherapy. J. Immunother. Cancer 2015, 3, 9. [Google Scholar] [CrossRef] [Green Version]
- Uehara, I.; Tanaka, N. Role of p53 in the Regulation of the Inflammatory Tumor Microenvironment and Tumor Suppression. Cancers 2018, 10, 219. [Google Scholar] [CrossRef] [Green Version]
- Wellenstein, M.D.; Coffelt, S.B.; Duits, D.E.M.; van Miltenburg, M.H.; Slagter, M.; de Rink, I.; Henneman, L.; Kas, S.M.; Prekovic, S.; Hau, C.S.; et al. Loss of p53 triggers Wnt-dependent systemic inflammation to drive breast cancer metastasis. Nature 2019, 572, 538–542. [Google Scholar] [CrossRef]
- Walton, J.; Blagih, J.; Ennis, D.; Leung, E.; Dowson, S.; Farquharson, M.; Tookman, L.A.; Orange, C.; Athineos, D.; Mason, S.; et al. CRISPR/Cas9-mediated Trp53 and Brca2 knockout to generate improved murine models of ovarian high grade serous carcinoma. Cancer Res. 2016, 76, 6118–6129. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Andrew, H.; Beck, I.E.; Edris, B.; Li, R.; Montgomery, K.; Zhu, S.; Varma, S.; Marinelli, R.J.; van de Rijn, M.; West, R.B. The Macrophage Colony Stimulating Factor-1 ResponseSignature in Breast Carcinoma. Clin. Cancer Res. 2009, 15, 778–787. [Google Scholar] [CrossRef] [Green Version]
- Blagih, J.; Zani, F.; Chakravarty, P.; Hennequart, M.; Pilley, S.; Hobor, S.; Hock, A.K.; Walton, J.B.; Morton, J.P.; Gronroos, E.; et al. Cancer-Specific Loss of p53 Leads to a Modulation of Myeloid and T Cell Responses. Cell Rep. 2020, 30, 481–496.e6. [Google Scholar] [CrossRef] [PubMed]
- Bezzi, M.; Seitzer, N.; Ishikawa, T.; Reschke, M.; Chen, M.; Wang, G.; Mitchell, C.; Ng, C.; Katon, J.; Lunardi, A.; et al. Diverse genetic-driven immune landscapes dictate tumor progression through distinct mechanisms. Nat Med. 2018, 24, 165–175. [Google Scholar] [CrossRef] [PubMed]
- Chen, Z.; Trotman, L.C.; Shaffer, D.; Lin, H.-K.; Dotan, Z.A.; Niki, M.; Koutcher, J.A.; Scher, H.I.; Ludwig, T.; Gerald, W.L.; et al. Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis. Nat. Cell Biol. 2005, 436, 725–730. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Iannello, A.; Thompson, T.W.; Ardolino, M.; Lowe, S.W.; Raulet, D.H. p53-dependent chemokine production by senescent tu-mor cells supports NKG2D-dependent tumor elimination by natural killer cells. J. Exp. Med. 2013, 210, 2057–2069. [Google Scholar] [CrossRef] [PubMed]
- Herranz, N.; Gallage, S.; Mellone, M.; Wuestefeld, T.; Klotz, S.; Hanley, C.J.; Raguz, S.; Acosta, J.C.; Innes, A.J.; Banito, A.; et al. mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype. Nat Cell Biol. 2015, 17, 1205–1217. [Google Scholar] [CrossRef] [Green Version]
- Laberge, R.-M.; Sun, Y.; Orjalo, A.V.; Patil, C.K.; Freund, A.; Zhou, L.; Curran, S.C.; Davalos, A.R.; Wilson-Edell, K.A.; Liu, S.; et al. MTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation. Nat. Cell Biol. 2015, 17, 1049–1061. [Google Scholar] [CrossRef]
- Stokes, K.L.; Cortez-Retamozo, V.; Acosta, J.; Lauderback, B.; Robles-Oteiza, C.; Cicchini, M.; Pittet, M.J.; Feldser, D.M. Natural killer cells limit the clearance of senescent lung adenocarcinoma cells. Oncogenesis 2019, 8, 1–13. [Google Scholar] [CrossRef]
- Hayden, S.; Ghosh, S. Regulation of NF-kappaB by TNF family cytokines. Semin. Immunol. 2014, 26, 253. [Google Scholar] [CrossRef] [Green Version]
- Komarova, E.A.; Krivokrysenko, V.; Wang, K.; Neznanov, N.; Chernov, M.V.; Komarov, P.G.; Brennan, M.L.; Golovkina, T.V.; Rokhlin, O.W.; Kuprash, D.V.; et al. p53 is a suppressor of inflammatory response in mice. FASEB J. 2005, 19, 1030–1032. [Google Scholar] [CrossRef]
- Cooks, T.; Pateras, I.S.; Jenkins, L.M.; Patel, K.M.; Robles, A.I.; Morris, J.; Forshew, T.; Appella, E.; Gorgoulis, V.G.; Harris, C.C. Mutant p53 cancers reprogram macrophages to tumor supporting macrophages via exosomal miR-1246. Nat. Commun. 2018, 9, 1–15. [Google Scholar] [CrossRef] [Green Version]
- Schwitalla, S.; Ziegler, P.K.; Horst, D.; Becker, V.; Kerle, I.; Begus-Nahrmann, Y.; Lechel, A.; Rudolph, K.L.; Langer, R.; Slotta-Huspenina, J.; et al. Loss of p53 in Enterocytes Generates an Inflammatory Microenvironment Enabling Invasion and Lymph Node Metastasis of Carcinogen-Induced Colorectal Tumors. Cancer Cell 2013, 23, 93–106. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Meylan, E.; Dooley, A.L.; Feldser, D.M.; Shen, L.; Turk, E.; Ouyang, C.; Jacks, T. Requirement for NF-kappaB signalling in a mouse model of lung adenocarcinoma. Nature 2009, 462, 104–107. [Google Scholar] [CrossRef]
- Spranger, S.; Bao, R.; Gajewski, T.F. Melanoma-intrinsic beta-catenin signalling prevents anti-tumour immunity. Nature 2015, 523, 231. [Google Scholar] [CrossRef]
- Luke, J.J.; Bao, R.; Sweis, R.F.; Spranger, S.; Gajewski, T.F. WNT/beta-catenin Pathway Activation Correlates with Immune Exclusion across Human Cancers. Clin. Cancer Res. 2019, 25, 3074. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Satpathy, A.T.; Wu, X.; Albring, J.C.; Murphy, K.M. Re(de)fining the dendritic cell lineage. Nat. Immunol. 2012, 13, 1145–1154. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Peng, W.; Chen, J.Q.; Liu, C.; Malu, S.; Creasy, C.; Tetzlaff, M.T.; Xu, C.; McKenzie, J.A.; Zhang, C.; Liang, X.; et al. Loss of PTEN Promotes Resistance to T Cell-Mediated Immunotherapy. Cancer Discov. 2016, 6, 202–216. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mateo, J.; Ganji, G.; Lemech, C.; Burris, H.A.; Han, S.W.; Swales, K.; Decordova, S.; DeYoung, M.P.; Smith, D.A.; Kalyana-Sundaram, S.; et al. A First-Time-in-Human Study of GSK2636771, a Phosphoinositide 3 Kinase Beta-Selective Inhibitor, in Patients with Advanced Solid Tumors. Clin. Cancer Res. 2017, 23, 5981–5992. [Google Scholar] [CrossRef] [Green Version]
- Peng, W.; Williams, L.J.; Xu, C.; Melendez, B.; McKenzie, J.A.; Chen, Y.; Jackson, H.L.; Voo, K.S.; Mbofung, R.M.; Leahey, S.E.; et al. Anti-OX40 Antibody Directly Enhances The Function of Tumor-Reactive CD8þT Cells and Synergizes with PI3KbInhibition in PTEN Loss Melanoma. Clin. Cancer Res. 2019, 25. [Google Scholar] [CrossRef] [Green Version]
- Conciatori, F.; Bazzichetto, C.; Falcone, I.; Ciuffreda, L.; Ferretti, G.; Vari, S.; Ferraresi, V.; Cognetti, F.; Milella, M. PTEN Function at the Interface between Cancer and Tumor Microenvironment: Implications for Response to Immunotherapy. Int. J. Mol. Sci. 2020, 21, 5337. [Google Scholar] [CrossRef]
- Kortlever, R.M.; Sodir, N.M.; Wilson, C.H.; Burkhart, D.L.; Pellegrinet, L.; Swigart, L.B.; Littlewood, T.D.; Evan, G.I. Myc Cooperates with Ras by Programming Inflammation and Immune Suppression. Cell 2017, 171, 1301–1315.e14. [Google Scholar] [CrossRef]
- Yetil, A.; Anchang, B.; Gouw, A.M.; Adam, S.J.; Zabuawala, T.; Parameswaran, R.; van Riggelen, J.; Plevritis, S.; Felsher, D.W. p19ARF is a critical mediator of both cellular senescence and an innate immune response associated with MYC inactivation in mouse model of acute leukemia. Oncotarget 2015, 6, 3563–3577. [Google Scholar] [CrossRef] [Green Version]
- Casey, S.C.; Tong, L.; Li, Y.; Do, R.; Walz, S.; Fitzgerald, K.N.; Gouw, A.M.; Baylot, V.; Gütgemann, I.; Eilers, M.; et al. MYC regulates the antitumor immune response through CD47 and PD-L1. Science 2016, 352, 227–231. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Layer, J.P.; Kronmüller, M.T.; Quast, T.; Boorn-Konijnenberg, D.V.D.; Effern, M.; Hinze, D.; Althoff, K.; Schramm, A.; Westermann, F.; Peifer, M.; et al. Amplification of N-Myc is associated with a T-cell-poor microenvironment in metastatic neuroblastoma restraining interferon pathway activity and chemokine expression. OncoImmunology 2017, 6, e1320626. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rakhra, K.; Bachireddy, P.; Zabuawala, T.; Zeiser, R.; Xu, L.; Kopelman, A.; Fan, A.C.; Yang, Q.; Braunstein, L.; Crosby, E.; et al. CD4(+) T cells contribute to the remodeling of the microenvironment required for sustained tumor regression upon oncogene inactivation. Cancer Cell 2010, 18, 485–498. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shchors, K.; Shchors, E.; Rostker, F.; Lawlor, E.R.; Brown-Swigart, L.; Evan, G.I. The Myc-dependent angiogenic switch in tumors is mediated by interleukin 1beta. Genes Dev. 2006, 20, 2527–2538. [Google Scholar] [CrossRef] [Green Version]
- Soucek, L.; Lawlor, E.R.; Soto, D.; Shchors, K.; Swigart, L.B.; Evan, G.I. Mast cells are required for angiogenesis and macroscopic expansion of Myc-induced pancreatic islet tumors. Nat. Med. 2007, 13, 1211–1218. [Google Scholar] [CrossRef] [PubMed]
- Deng, S.; Clowers, M.J.; Velasco, W.V.; Ramos-Castaneda, M.; Moghaddam, S.J. Understanding the Complexity of the Tumor Microenvironment in K-ras Mutant Lung Cancer: Finding an Alternative Path to Prevention and Treatment. Front. Oncol. 2020, 9, 1556. [Google Scholar] [CrossRef] [PubMed]
- Sparmann, A.; Bar-Sagi, D. Ras-induced interleukin-8 expression plays a critical role in tumor growth and angiogenesis. Cancer Cell 2004, 6, 447. [Google Scholar] [CrossRef] [Green Version]
- Ancrile, K.; Lim, H.; Counter, C.M. Oncogenic Ras-induced secretion of IL6 is required for tumorigenesis. Genes Dev. 2007, 21, 1714. [Google Scholar] [CrossRef] [Green Version]
- Pylayeva-Gupta, Y.; Lee, K.E.; Hajdu, C.H.; Miller, G.; Bar-Sagi, D. Oncogenic Kras-Induced GM-CSF Production Promotes the Development of Pancreatic Neoplasia. Cancer Cell 2012, 21, 836–847. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dong, Z.Y.; Zhong, W.Z.; Zhang, X.C.; Su, J.; Xie, Z.; Liu, S.Y.; Tu, H.Y.; Chen, H.J.; Sun, Y.L.; Zhou, Q.; et al. Potential Predictive Value of TP53 and KRAS Mutation Status for Response to PD-1 Blockade Immunotherapy in Lung Adenocarcinoma. Clin. Cancer Res. 2017, 23, 3012–3024. [Google Scholar] [CrossRef] [Green Version]
- Lee, C.K.; Man, J.; Lord, S.; Cooper, W.; Links, M.; Gebski, V.; Herbst, R.S.; Gralla, R.J.; Mok, T.; Yang, J.C. Clinical and Molecular Characteristics Associated with Survival among Patients Treated with Checkpoint Inhibitors for Advanced Non-Small Cell Lung Carcinoma: A Systematic Review and Meta-analysis. JAMA Oncol. 2018, 4, 210–216. [Google Scholar] [CrossRef]
- Wislez, M.; Fujimoto, N.; Izzo, J.G.; Hanna, A.E.; Cody, D.D.; Langley, R.R.; Tang, H.; Burdick, M.D.; Sato, M.; Minna, J.D.; et al. High expression of ligands for chemokine receptor CXCR2 in alveolar epithelial neoplasia induced by oncogenic kras. Cancer Res. 2006, 66, 4198–4207. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhou, J.; Qu, Z.; Sun, F.; Han, L.; Li, L.; Yan, S.; Stabile, L.P.; Chen, L.F.; Siegfried, J.M.; Xiao, G. Myeloid STAT3 Promotes Lung Tumorigenesis by Transforming Tumor Immunosurveillance into Tumor-Promoting Inflammation. Cancer Immunol. Res. 2017, 5, 257–268. [Google Scholar] [CrossRef] [Green Version]
- Karin, M. Inflammation and cancer: The long reach of Ras. Nat. Med. 2005, 11, 20–21. [Google Scholar] [CrossRef] [PubMed]
- Busch, S.E.; Hanke, M.L.; Kargl, J.; Metz, H.E.; MacPherson, D.; Houghton, A.M. Lung Cancer Subtypes Generate Unique Immune Responses. J. Immunol. 2016, 197, 4493–4503. [Google Scholar] [CrossRef] [Green Version]
- Frese, K.K.; Tuveson, D.A. Maximizing mouse cancer models. Nat. Rev. Cancer 2007, 7, 654–658. [Google Scholar] [CrossRef] [PubMed]
- Yamaguchi, R.; Perkins, G. Animal models for studying tumor microenvironment (TME) and resistance to lymphocytic infiltration. Cancer Biol. Ther. 2018, 19, 745–754. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ikeda, H.; Old, L.J.; Schreiber, R.D. The roles of IFNγ in protection against tumor development and cancer immunoediting. Cytokine Growth Factor Rev. 2002, 13, 95. [Google Scholar] [CrossRef]
- Overwijk, W.W.; Restifo, N.P. B16 as a Mouse Model for Human Melanoma. Curr. Protoc. Immunol. 2000, 39, 20.1.1–20.1.29. [Google Scholar] [CrossRef] [PubMed]
- Lesokhin, A.M.; Hohl, T.M.; Kitano, S.; Cortez, C.; Hirschhorn-Cymerman, D.; Avogadri, F.; Rizzuto, G.A.; Lazarus, J.J.; Pamer, E.G.; Houghton, A.N.; et al. Monocytic CCR2(+) myeloid-derived suppressor cells promote immune escape by limiting activated CD8 T-cell infiltration into the tumor microenvironment. Cancer Res. 2012, 72, 876–886. [Google Scholar] [CrossRef] [Green Version]
- Youn, J.-I.; Nagaraj, S.; Collazo, M.; Gabrilovich, D.I. Subsets of Myeloid-Derived Suppressor Cells in Tumor-Bearing Mice. J. Immunol. 2008, 181, 5791–5802. [Google Scholar] [CrossRef]
- O’Hagan, R.C.; Heyer, J. KRAS Mouse Models: Modeling Cancer Harboring KRAS Mutations. Genes Cancer 2011, 2, 335–343. [Google Scholar] [CrossRef]
- Piechocki, M.P.; Ho, Y.-S.; Pilon, S.; Wei, W.-Z. Human ErbB-2 (Her-2) transgenic mice: A model system for testing Her-2 based vaccines. J. Immunol. 2003, 171, 5787–5794. [Google Scholar] [CrossRef] [Green Version]
- Fischer, M. Mice Are Not Humans: The Case of p53. Trends Cancer 2021, 7, 12–14. [Google Scholar] [CrossRef]
- Altorki, N.K.; Markowitz, G.J.; Gao, D.; Port, J.L.; Saxena, A.; Stiles, B.; McGraw, T.; Mittal, V. The lung microenvironment: An important regulator of tumour growth and metastasis. Nat. Rev. Cancer 2019, 19, 9–31. [Google Scholar] [CrossRef] [Green Version]
- Messmer, M.N.; Netherby, C.S.; Banik, D.; Abrams, S.I. Tumor-induced myeloid dysfunction and its implications for cancer immunotherapy. Cancer Immunol. Immunother. 2015, 64, 1–13. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Almatroodi, S.A.; McDonald, C.F.; Darby, I.A.; Pouniotis, D.S. Characterization of M1/M2 Tumour-Associated Macrophages (TAMs) and Th1/Th2 Cytokine Profiles in Patients with NSCLC. Cancer Microenviron. 2016, 9, 1. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tucci, M.; Passarelli, A.; Mannavola, F.; Felici, C.; Stucci, L.S.; Cives, M.; Silvestris, F. Immune System Evasion as Hallmark of Melanoma Progression: The Role of Dendritic Cells. Front. Oncol. 2019, 9, 1148. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Turkes, F.; Mencel, J.; Starling, N. Targeting the immune milieu in gastrointestinal cancers. J. Gastroenterol. 2020, 55, 909. [Google Scholar] [CrossRef]
- Vladutiu, A.O. The severe combined immunodeficient (SCID) mouse as a model for the study of autoimmune diseases. Clin. Exp. Immunol. 1993, 93, 1–8. [Google Scholar] [CrossRef] [PubMed]
- Ito, M.; Hiramatsu, H.; Kobayashi, K.; Suzue, K.; Kawahata, M.; Hioki, K.; Ueyama, Y.; Koyanagi, Y.; Sugamura, K.; Tsuji, K.; et al. NOD/SCID/gamma(c)(null) mouse: An excellent recipient mouse model for engraftment of human cells. Blood. 2002, 100, 3175–3182. [Google Scholar] [CrossRef]
- Audigé, A.; Rochat, M.A.; Li, D.; Ivic, S.; Farhny, A.; Muller, C.K.; Gers-Huber, G.; Myburgh, R.; Bredl, S.; Schlaepfer, E.; et al. Long-term leukocyte reconstitution in NSG mice transplanted with human cord blood hematopoietic stem and progenitor cells. BMC Immunol. 2017. [Google Scholar] [CrossRef]
- Bhimani, J.; Ball, K.; Stebbing, J. Patient-derived xenograft models—the future of personalised cancer treatment. Br. J. Cancer 2020, 122, 601–602. [Google Scholar] [CrossRef]
- Ashraf, Y.; Mansouri, H.; Laurent-Matha, V.; Alcaraz, L.B.; Roger, P.; Guiu, S.; Derocq, D.; Robin, G.; Michaud, H.-A.; Delpech, H.; et al. Immunotherapy of triple-negative breast cancer with cathepsin D-targeting antibodies. J. Immunother. Cancer 2019, 7, 29. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Welte, T.; Kim, I.S.; Tian, L.; Gao, X.; Wang, H.; Li, J.; Holdman, X.B.; Herschkowitz, J.I.; Pond, A.; Xie, G.; et al. Oncogenic mTOR signalling recruits myeloid-derived suppressor cells to promote tumour initiation. Nat. Cell Biol. 2016, 18, 632–644. [Google Scholar] [CrossRef] [Green Version]
- Cha, Y.J.; Koo, J.S. Role of Tumor-Associated Myeloid Cells in Breast Cancer. Cells 2020, 9, 1785. [Google Scholar] [CrossRef] [PubMed]
- Kim, J.; Koo, B.-K.; Knoblich, J.A. Human organoids: Model systems for human biology and medicine. Nat. Rev. Mol. Cell Biol. 2020, 21, 1–14. [Google Scholar] [CrossRef]
- Horvath, P.; Aulner, N.; Bickle, M.; Davies, A.M.; Del Nery, E.; Ebner, D.; Montoya, M.C.; Östling, P.; Pietiäinen, V.; Price, L.S.; et al. Screening out irrelevant cell-based models of disease. Nat. Rev. Drug Discov. 2016, 15, 751–769. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sun, L.; Zhang, L.; Yu, J.; Zhang, Y.; Pang, X.; Ma, C.; Shen, M.; Ruan, S.; Wasan, H.S.; Qiu, S. Clinical efficacy and safety of anti-PD-1/PD-L1 inhibitors for the treatment of advanced or metastatic cancer: A systematic review and meta-analysis. Sci. Rep. 2020, 10, 1–13. [Google Scholar] [CrossRef] [Green Version]
- Bibby, M. Orthotopic models of cancer for preclinical drug evaluation: Advantages and disadvantages. Eur. J. Cancer 2004, 40, 852–857. [Google Scholar] [CrossRef] [PubMed]
- Santo, V.E.; Estrada, M.F.; Rebelo, S.P.; Abreu, S.; Silva, I.; Pinto, C.; Veloso, S.C.; Serra, A.T.; Boghaert, E.; Alves, P.M.; et al. Adaptable stirred-tank culture strategies for large scale production of multicellular spheroid-based tumor cell models. J. Biotechnol. 2016, 221, 118–129. [Google Scholar] [CrossRef]
- Benien, P.; Swami, A. 3D tumor models: History, advances and future perspectives. Future Oncol. 2014, 10, 1311–1327. [Google Scholar] [CrossRef] [PubMed]
- Breslin, S.; O’Driscoll, L. Three-dimensional cell culture: The missing link in drug discovery. Drug Discov. Today 2013, 18, 240–249. [Google Scholar] [CrossRef]
- Lin, R.Z.; Chang, H.Y. Recent advances in three-dimensional multicellular spheroid culture for biomedical research. Biotecnol. J. 2008, 3, 1172. [Google Scholar] [CrossRef] [PubMed]
- Pinto, B.; Henriques, A.C.; Silva, P.M.A.; Bousbaa, H. Three-Dimensional Spheroids as In Vitro Preclinical Models for Cancer Research. Pharmaceutics 2020, 12, 1186. [Google Scholar] [CrossRef]
- Saraiva, D.P.; Matias, A.T.; Braga, S.; Jacinto, A.; Cabral, M.G. Establishment of a 3D Co-culture With MDA-MB-231 Breast Cancer Cell Line and Patient-Derived Immune Cells for Application in the Development of Immunotherapies. Front. Oncol. 2020, 10, 1543. [Google Scholar] [CrossRef] [PubMed]
- Courau, T.; Bonnereau, J.; Chicoteau, J.; Bottois, H.; Remark, R.; Assante Miranda, L.; Toubert, A.; Blery, M.; Aparicio, T.; Allez, M.; et al. Cocultures of human colorectal tumor spheroids with immune cells reveal the therapeutic potential of MICA/B and NKG2A targeting for cancer treatment. J. Immunother. Cancer 2019, 7, 74. [Google Scholar] [CrossRef] [Green Version]
- Rebelo, S.P.; Pinto, C.; Martins, T.R.; Harrer, N.; Estrada, M.F.; Loza-Alvarez, P.; Cabeçadas, J.; Alves, P.M.; Gualda, E.J.; Sommergruber, W.; et al. 3D-3-culture: A tool to unveil macrophage plasticity in the tumour microenvironment. Biomaterials 2018, 163, 185–197. [Google Scholar] [CrossRef]
- Yuki, K.; Cheng, N.; Nakano, M.; Kuo, C.J. Organoid Models of Tumor Immunology. Trends Immunol. 2020, 41, 652–664. [Google Scholar] [CrossRef]
- McCauley, A.; Wells, J.M. Pluripotent stem cell-derived organoids: Using principles of developmental biology to grow human tissues in a dish. Development 2017, 144, 958. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Driehuis, E.; Kretzschmar, K.; Clevers, H. Author Correction: Establishment of patient-derived cancer organoids for drug-screening applications. Nat. Protoc. 2021, 15, 3380. [Google Scholar] [CrossRef]
- Yao, Y.; Xu, X.; Yang, L.; Zhu, J.; Wan, J.; Shen, L.; Xia, F.; Fu, G.; Deng, Y.; Pan, M.; et al. Patient-Derived Organoids Predict Chemoradiation Responses of Locally Advanced Rectal Cancer. Cell Stem Cell 2020, 26, 17–26.e16. [Google Scholar] [CrossRef]
- Ganesh, K.; Wu, C.; O’Rourke, K.P.; Szeglin, B.C.; Zheng, Y.; Sauvé, C.-E.G.; Adileh, M.; Wasserman, I.; Marco, M.R.; Kim, A.S.; et al. A rectal cancer organoid platform to study individual responses to chemoradiation. Nat. Med. 2019, 25, 1607–1614. [Google Scholar] [CrossRef]
- Sachs, N.; De Ligt, J.; Kopper, O.; Gogola, E.; Bounova, G.; Weeber, F.; Balgobind, A.V.; Wind, K.; Gracanin, A.; Begthel, H.; et al. A Living Biobank of Breast Cancer Organoids Captures Disease Heterogeneity. Cell 2018, 172, 373–386.e10. [Google Scholar] [CrossRef] [Green Version]
- Campaner, E.; Zannini, A.; Santorsola, M.; Bonazza, D.; Bottin, C.; Cancila, V.; Tripodo, C.; Bortul, M.; Zanconati, F.; Schoeftner, S.; et al. Breast Cancer Organoids Model Patient-Specific Response to Drug Treatment. Cancers 2020, 12, 3869. [Google Scholar] [CrossRef]
- Mimoto, R.; Yogosawa, S.; Saijo, H.; Fushimi, A.; Nogi, H.; Asakura, T.; Yoshida, K.; Takeyama, H. Clinical implications of drug-screening assay for recurrent metastatic hormone receptor-positive, human epidermal receptor 2-negative breast cancer using conditionally reprogrammed cells. Sci. Rep. 2019, 9, 13405. [Google Scholar] [CrossRef] [PubMed]
- Saito, Y.; Muramatsu, T.; Kanai, Y.; Ojima, H.; Sukeda, A.; Hiraoka, N.; Arai, E.; Sugiyama, Y.; Matsuzaki, J.; Uchida, R.; et al. Establishment of Patient-Derived Organoids and Drug Screening for Biliary Tract Carcinoma. Cell Rep. 2019, 27, 1265–1276.e4. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Khetani, R. Pluripotent Stem Cell-Derived Human Liver Organoids Enter the Realm of High-Throughput Drug Screening. Gastroenterology 2021, 160, 653. [Google Scholar] [CrossRef] [PubMed]
- Akbari, S.; Arslan, N.; Senturk, S.; Erdal, E. Next-Generation Liver Medicine Using Organoid Models. Front. Cell Dev. Biol. 2019, 7, 345. [Google Scholar] [CrossRef]
- Sgodda, M.; Dai, Z.; Zweigerdt, R.; Sharma, A.D.; Ott, M.; Cantz, T. A Scalable Approach for the Generation of Human Pluripotent Stem Cell-Derived Hepatic Organoids with Sensitive Hepatotoxicity Features. Stem Cells Dev. 2017, 26, 1490–1504. [Google Scholar] [CrossRef]
- Driehuis, E.; Van Hoeck, A.; Moore, K.; Kolders, S.; Francies, H.E.; Gulersonmez, M.C.; Stigter, E.C.A.; Burgering, B.; Geurts, V.; Gracanin, A.; et al. Pancreatic cancer organoids recapitulate disease and allow personalized drug screening. Proc. Natl. Acad. Sci. USA 2019, 116, 26580–26590. [Google Scholar] [CrossRef] [PubMed]
- Wills, E.S.; Drenth, J.P.H. Building pancreatic organoids to aid drug development. Gut 2016, 66, 393–394. [Google Scholar] [CrossRef]
- Huang, L.; Holtzinger, A.; Jagan, I.; BeGora, M.; Lohse, I.; Ngai, N.; Nostro, C.; Wang, R.; Muthuswamy, L.B.; Crawford, H.C.; et al. Ductal pancreatic cancer modeling and drug screening using human pluripotent stem cell– and patient-derived tumor organoids. Nat. Med. 2015, 21, 1364–1371. [Google Scholar] [CrossRef]
- Hou, S.; Tiriac, H.; Sridharan, B.P.; Scampavia, L.; Madoux, F.; Seldin, J.; Souza, G.R.; Watson, D.; Tuveson, D.; Spicer, T.P. Advanced Development of Primary Pancreatic Organoid Tumor Models for High-Throughput Phenotypic Drug Screening. SLAS Discov. 2018, 23, 574–584. [Google Scholar] [CrossRef] [Green Version]
- Henrik Renner, M.G.; Becker, K.J.; Kagermeier, T.E.; Wu, J.; Otto, M.; Peischard, S.; Zeuschner, D.; TsyTsyura, Y.; Disse, P.; Klingauf, J.; et al. A fully automated high-throughput workflow for 3D-based chemical screening in human midbrain organoids. eLife 2020. [Google Scholar] [CrossRef]
- Linkous, A.; Balamatsias, D.; Snuderl, M.; Edwards, L.; Miyaguchi, K.; Milner, T.; Reich, B.; Cohen-Gould, L.; Storaska, A.; Nakayama, Y.; et al. Modeling Patient-Derived Glioblastoma with Cerebral Organoids. Cell Rep. 2019, 26, 3203–3211. [Google Scholar] [CrossRef] [Green Version]
- Chadwick, M.; Yang, C.; Liu, L.; Gamboa, C.M.; Jara, K.; Lee, H.; Sabaawy, H.E. Rapid Processing and Drug Evaluation in Glioblastoma Patient-Derived Organoid Models with 4D Bioprinted Arrays. iScience 2020, 23, 101365. [Google Scholar] [CrossRef] [PubMed]
- Ogawa, J.; Pao, G.M.; Shokhirev, M.N.; Verma, I.M. Glioblastoma Model Using Human Cerebral Organoids. Cell Rep. 2018, 23, 1220–1229. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bian, S.; Repic, M.; Guo, Z.; Kavirayani, A.; Burkard, T.; Bagley, J.A.; Krauditsch, C.; Knoblich, J.A. Genetically engineered cerebral organoids model brain tumor formation. Nat Methods. 2018, 15, 631–639. [Google Scholar] [CrossRef]
- Andreatta, F.; Beccaceci, G.; Fortuna, N.; Celotti, M.; De Felice, D.; Lorenzoni, M.; Foletto, V.; Genovesi, S.; Rubert, J.; Alaimo, A. The Organoid Era Permits the Development of New Applications to Study Glioblastoma. Cancers 2020, 12, 3303. [Google Scholar] [CrossRef] [PubMed]
- Neal, J.T.; Li, X.; Zhu, J.; Giangarra, V.; Grzeskowiak, C.L.; Ju, J.; Liu, I.H.; Chiou, S.H.; Salahudeen, A.A.; Smith, A.R.; et al. Organoid Modeling of the Tumor Immune Microenvironment. Cell 2018, 175, 1972–1988. [Google Scholar] [CrossRef] [Green Version]
- Drost, J.; Van Jaarsveld, R.H.; Ponsioen, B.; Zimberlin, C.; Van Boxtel, R.; Buijs, A.; Sachs, N.; Overmeer, R.M.; Offerhaus, G.J.; Begthel, H.; et al. Sequential cancer mutations in cultured human intestinal stem cells. Nature 2015, 521, 43–47. [Google Scholar] [CrossRef] [PubMed]
- Fujii, M.; Shimokawa, M.; Date, S.; Takano, A.; Matano, M.; Nanki, K.; Ohta, Y.; Toshimitsu, K.; Nakazato, Y.; Kawasaki, K.; et al. A Colorectal Tumor Organoid Library Demonstrates Progressive Loss of Niche Factor Requirements during Tumorigenesis. Cell Stem Cell 2016, 18, 827–838. [Google Scholar] [CrossRef] [Green Version]
- Chakrabarti, J.; Holokai, L.; Syu, L.; Steele, N.G.; Chang, J.; Wang, J.; Ahmed, S.; Dlugosz, A.; Zavros, Y. Hedgehog signaling induces PD-L1 expression and tumor cell proliferation in gastric cancer. Oncotarget 2018, 9, 37439–37457. [Google Scholar] [CrossRef] [Green Version]
- Chakrabarti, J.; Holokai, L.; Syu, L.; Steele, N.; Chang, J.; Dlugosz, A.; Zavros, Y. Mouse-Derived Gastric Organoid and Immune Cell Co-culture for the Study of the Tumor Microenvironment. Methods Mol. Biol. 2018, 1817, 157–168. [Google Scholar] [CrossRef] [PubMed]
- Teal, E.; Steele, N.G.; Chakrabarti, J.; Holokai, L.; Zavros, Y. Mouse- and Human-derived Primary Gastric Epithelial Monolayer Culture for the Study of Regeneration. J. Vis. Exp. 2018, e57435. [Google Scholar] [CrossRef]
- Holokai, L.; Chakrabarti, J.; Broda, T.; Chang, J.; Hawkins, J.A.; Sundaram, N.; Wroblewski, L.E.; Peek, R.M., Jr.; Wang, J.; Helmrath, M.; et al. Increased Programmed Death-Ligand 1 is an Early Epithelial Cell Response to Helicobacter pylori Infection. PLoS Pathog. 2019, 15, e1007468. [Google Scholar] [CrossRef] [Green Version]
- Holokai, L.; Chakrabarti, J.; Lundy, J.; Croagh, D.; Adhikary, P.; Richards, S.S.; Woodson, C.; Steele, N.; Kuester, R.; Scott, A.; et al. Murine- and Human-Derived Autologous Organoid/Immune Cell Co-Cultures as Pre-Clinical Models of Pancreatic Ductal Adenocarcinoma. Cancers 2020, 12, 3816. [Google Scholar] [CrossRef]
- Dijkstra, K.K.; Cattaneo, C.M.; Weeber, F.; Chalabi, M.; Van De Haar, J.; Fanchi, L.F.; Slagter, M.; Van Der Velden, D.L.; Kaing, S.; Kelderman, S.; et al. Generation of Tumor-Reactive T Cells by Co-culture of Peripheral Blood Lymphocytes and Tumor Organoids. Cell 2018, 174, 1586–1598. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cattaneo, C.M.; Dijkstra, K.K.; Fanchi, L.F.; Kelderman, S.; Kaing, S.; van Rooij, N.; van den Brink, S.; Schumacher, T.N.; Voest, E.E. Tumor organoid-T-cell coculture systems. Nat. Protoc. 2020, 15–39. [Google Scholar] [CrossRef]
- Ootani, A.; Li, X.; Sangiorgi, E.; Ho, Q.T.; Ueno, H.; Toda, S.; Sugihara, H.; Fujimoto, K.; Weissman, I.L.; Capecchi, M.R.; et al. Sustained in vitro intestinal epithelial culture within a Wnt-dependent stem cell niche. Nat. Med. 2009, 701–706. [Google Scholar] [CrossRef] [Green Version]
- Li, X.; Ootani, A.; Kuo, C. An Air-Liquid Interface Culture System for 3D Organoid Culture of Diverse Primary Gastrointes-tinal Tissues. Methods Mol. Biol. 2016, 1422, 33. [Google Scholar]
- Jenkins, R.W.; Aref, A.R.; Lizotte, P.H.; Ivanova, E.; Stinson, S.; Zhou, C.W.; Bowden, M.; Deng, J.; Liu, H.; Miao, D.; et al. Ex Vivo Profiling of PD-1 Blockade Using Organotypic Tumor Spheroids. Cancer Discov. 2018, 8, 196–215. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lou, Y.-R.; Leung, A.W. Next generation organoids for biomedical research and applications. Biotechnol. Adv. 2018, 36, 132–149. [Google Scholar] [CrossRef] [PubMed]
- Boussommier-Calleja, A.; Li, R.; Chen, M.B.; Wong, S.C.; Kamm, R.D. Microfluidics: A New Tool for Modeling Cancer–Immune Interactions. Trends Cancer 2016, 2, 6–19. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cui, X.; Morales, R.-T.T.; Qian, W.; Wang, H.; Gagner, J.-P.; Dolgalev, I.; Placantonakis, D.; Zagzag, D.; Cimmino, L.; Snuderl, M.; et al. Hacking macrophage-associated immunosuppression for regulating glioblastoma angiogenesis. Biomaterials 2018, 161, 164–178. [Google Scholar] [CrossRef]
- Agliari, E.; Biselli, E.; De Ninno, A.; Schiavoni, G.; Gabriele, L.; Gerardino, A.; Mattei, F.; Barra, A.; Businaro, L. Cancer-driven dynamics of immune cells in a microfluidic environment. Sci. Rep. 2014, 4. [Google Scholar] [CrossRef]
- Baker, K. Organoids Provide an Important Window on Inflammation in Cancer. Cancers 2018, 10, 151. [Google Scholar] [CrossRef] [Green Version]
- Peng, D.; Kryczek, I.; Nagarsheth, N.; Zhao, L.; Wei, S.; Wang, W.; Sun, Y.; Zhao, E.; Vatan, L.; Szeliga, W.; et al. Epigenetic silencing of TH1-type chemokines shapes tumour immunity and immunotherapy. Nat. Cell Biol. 2015, 527, 249–253. [Google Scholar] [CrossRef] [Green Version]
- Zingg, D.; Arenas-Ramirez, N.; Sahin, D.; Rosalia, R.A.; Antunes, A.T.; Haeusel, J.; Sommer, L.; Boyman, O. The Histone Methyltransferase Ezh2 Controls Mechanisms of Adaptive Resistance to Tumor Immunotherapy. Cell Rep. 2017, 854–867. [Google Scholar] [CrossRef] [PubMed] [Green Version]
Tumor Model | Immune Cell Types Associated with Poor Survival | References |
---|---|---|
Lung | tumor-associated macrophages (TAMs), T-regulatory cells (T-regs), myeloid-derived suppressor cells (MDSCs) | [85,86,87] |
Melanoma | tumor-associated macrophages (TAMs), T-regulatory cells (T-regs), myeloid-derived suppressor cells (MDSCs) | [88] |
Gastric | T-regulatory cells (T-regs), myeloid-derived suppressor cells (MDSCs) | [89] |
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Ho, T.; Msallam, R. Tissues and Tumor Microenvironment (TME) in 3D: Models to Shed Light on Immunosuppression in Cancer. Cells 2021, 10, 831. https://doi.org/10.3390/cells10040831
Ho T, Msallam R. Tissues and Tumor Microenvironment (TME) in 3D: Models to Shed Light on Immunosuppression in Cancer. Cells. 2021; 10(4):831. https://doi.org/10.3390/cells10040831
Chicago/Turabian StyleHo, Teresa, and Rasha Msallam. 2021. "Tissues and Tumor Microenvironment (TME) in 3D: Models to Shed Light on Immunosuppression in Cancer" Cells 10, no. 4: 831. https://doi.org/10.3390/cells10040831
APA StyleHo, T., & Msallam, R. (2021). Tissues and Tumor Microenvironment (TME) in 3D: Models to Shed Light on Immunosuppression in Cancer. Cells, 10(4), 831. https://doi.org/10.3390/cells10040831