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Frontiers in Immuno-Oncology
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Frontiers in Immuno-Oncology

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 15731

Special Issue Editors

Dr. Cinzia Solinas

E-Mail Website
Guest Editor
Medical Oncology, Azienda Tutela della Salute Sardegna, San Francesco Hospital, 08100 Nuoro, Italy
Interests: immune-related pneumonitis; immune-related hypophysitis; immune-related pancreatitis; immunotherapy; radiology and immunotherapy; breast cancer; tumor-infiltrating lymphocytes; tertiary lymphoid structures
Dr. Pushpamali de Silva

E-Mail Website
Guest Editor
Wellman Center for Photomedicine, Department of Dermatology, Harvard Medical School and Massachusetts General Hospital, Boston, MA, USA
Interests: immune

Special Issue Information

Dear Colleagues,

Immunotherapy represents one of the mainstays of cancer treatment particularly after the introduction of immune checkpoint blockade.  Manipulating the immune response against the tumor has gained success in patients with various tumors, generating lasting responses and increasing the chances of cure. An in depht knowledge of the immuno-biology, on patient selection (e.g. through biomarkers), on the management of immunotherapy associated side effects, on the evaluation of the response to these novel treatments is necessary for every clinician. Aim of this special issue is to provide an overview and an update on immuno oncology achievements with a multidisciplinary approach.

Dr. Cinzia Solinas
Dr. Pushpamali de Silva
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • immune checkpoint blockade
  • immune-related adverse events
  • immuno-biology
  • imaging
  • immune biomarkers

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Published Papers (4 papers)

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Research

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14 pages, 2800 KiB  
Article
A Combination of Chemotherapy and Oncolytic Virotherapy Sensitizes Colorectal Adenocarcinoma to Immune Checkpoint Inhibitors in a cDC1-Dependent Manner
by Nader El-Sayes, Alyssa Vito, Omar Salem, Samuel Tekeste Workenhe, Yonghong Wan and Karen Mossman
Int. J. Mol. Sci. 2022, 23(3), 1754; https://doi.org/10.3390/ijms23031754 - 3 Feb 2022
Cited by 10 | Viewed by 3088
Abstract
Immune checkpoint therapy has shown great promise in the treatment of cancers with a high mutational burden, such as mismatch repair-deficient colorectal carcinoma (dMMR CRC). However, many patients fail to respond to immune checkpoint therapy. Using a mouse model of dMMR CRC, we [...] Read more.
Immune checkpoint therapy has shown great promise in the treatment of cancers with a high mutational burden, such as mismatch repair-deficient colorectal carcinoma (dMMR CRC). However, many patients fail to respond to immune checkpoint therapy. Using a mouse model of dMMR CRC, we demonstrated that tumors can be further sensitized to immune checkpoint therapy by using a combination of low-dose chemotherapy and oncolytic HSV-1. This combination induced the infiltration of CD8+ and CD4+ T cells into the tumor and the upregulation of gene signatures associated with the chemoattraction of myeloid cell subsets. When combined with immune checkpoint therapy, the combination promoted the infiltration of activated type 1 conventional dendritic cells (cDC1s) into the tumor. Furthermore, we found this combination strategy to be dependent on cDC1s, and its therapeutic efficacy to be abrogated in cDC1-deficient Batf3−/− mice. Thus, we demonstrated that the adjuvanticity of dMMR CRCs can be improved by combining low-dose chemotherapy and oncolytic HSV-1 in a cDC1-dependent manner. Full article
(This article belongs to the Special Issue Frontiers in Immuno-Oncology)
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19 pages, 1945 KiB  
Article
The Enhanced Cytotoxic Effects in B-Cell Leukemia and Lymphoma Following Activation of Prostaglandin EP4 Receptor and Targeting of CD20 Antigen by Monoclonal Antibodies
by Tijana Markovič, Helena Podgornik, Damjan Avsec, Sanja Nabergoj and Irena Mlinarič-Raščan
Int. J. Mol. Sci. 2022, 23(3), 1599; https://doi.org/10.3390/ijms23031599 - 29 Jan 2022
Viewed by 2367
Abstract
Anti-CD20 monoclonal antibodies (MAbs) have revolutionized the treatment of B-cell leukemia and lymphoma. However, many patients do not respond to such treatment due to either deficiency of the complementary immune response or resistance to apoptosis. Other currently available treatments are often inadequate or [...] Read more.
Anti-CD20 monoclonal antibodies (MAbs) have revolutionized the treatment of B-cell leukemia and lymphoma. However, many patients do not respond to such treatment due to either deficiency of the complementary immune response or resistance to apoptosis. Other currently available treatments are often inadequate or induce major side effects. Therefore, there is a constant need for improved therapies. The prostaglandin E2 receptor 4 (EP4) receptor has been identified as a promising therapeutic target for hematologic B-cell malignancies. Herein, we report that EP4 receptor agonists PgE1-OH and L-902688 have exhibited enhanced cytotoxicity when applied together with anti-CD20 MAbs rituximab, ofatumumab and obinutuzumab in vitro in Burkitt lymphoma cells Ramos, as well as in p53-deficient chronic lymphocytic leukemia (CLL) cells MEC-1. Moreover, the enhanced cytotoxic effects of EP4 receptor agonists and MAbs targeting CD20 have been identified ex vivo on primary lymphocytes B obtained from patients diagnosed with CLL. Incubation of cells with PgE1-OH and L-902688 preserved the expression of CD20 molecules, further confirming the anti-leukemic potential of EP4 receptor agonists in combination with anti-CD20 MAbs. Additionally, we demonstrated that the EP4 receptor agonist PgE-1-OH induced apoptosis and inhibited proliferation via the EP4 receptor triggering in CLL. This work has revealed very important findings leading towards the elucidation of the anticancer potential of PgE1-OH and L-902688, either alone or in combination with MAbs. This may contribute to the development of potential therapeutic alternatives for patients with B-cell malignancies. Full article
(This article belongs to the Special Issue Frontiers in Immuno-Oncology)
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14 pages, 2478 KiB  
Article
DFMO Improves Survival and Increases Immune Cell Infiltration in Association with MYC Downregulation in the Pancreatic Tumor Microenvironment
by Sai Preethi Nakkina, Sarah B. Gitto, Jordan M. Beardsley, Veethika Pandey, Michael W. Rohr, Jignesh G. Parikh, Otto Phanstiel IV and Deborah A. Altomare
Int. J. Mol. Sci. 2021, 22(24), 13175; https://doi.org/10.3390/ijms222413175 - 7 Dec 2021
Cited by 4 | Viewed by 4690
Abstract
Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor five-year survival rate of less than 10%. Immune suppression along with chemoresistance are obstacles for PDAC therapeutic treatment. Innate immune cells, such as tumor-associated macrophages, are recruited to the inflammatory environment of PDAC and adversely [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor five-year survival rate of less than 10%. Immune suppression along with chemoresistance are obstacles for PDAC therapeutic treatment. Innate immune cells, such as tumor-associated macrophages, are recruited to the inflammatory environment of PDAC and adversely suppress cytotoxic T lymphocytes. KRAS and MYC are important oncogenes associated with immune suppression and pose a challenge to successful therapies. Here, we targeted KRAS, through inhibition of downstream c-RAF with GW5074, and MYC expression via difluoromethylornithine (DFMO). DFMO alone and with GW5074 reduced in vitro PDAC cell viability. Both DFMO and GW5074 showed efficacy in reducing in vivo PDAC growth in an immunocompromised model. Results in immunocompetent syngeneic tumor-bearing mice showed that DFMO and combination treatment markedly decreased tumor size, but only DFMO increased survival in mice. To further investigate, immunohistochemical staining showed DFMO diminished MYC expression and increased tumor infiltration of macrophages, CD86+ cells, CD4+ and CD8+ T lymphocytes. GW5074 was not as effective in modulating the tumor infiltration of total CD3+ lymphocytes or tumor progression and maintained MYC expression. Collectively, this study highlights that in contrast to GW5074, the inhibition of MYC through DFMO may be an effective treatment modality to modulate PDAC immunosuppression. Full article
(This article belongs to the Special Issue Frontiers in Immuno-Oncology)
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Review

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25 pages, 2331 KiB  
Review
Tumor-Derived Exosomes in Tumor-Induced Immune Suppression
by Qiongyu Hao, Yong Wu, Yanyuan Wu, Piwen Wang and Jaydutt V. Vadgama
Int. J. Mol. Sci. 2022, 23(3), 1461; https://doi.org/10.3390/ijms23031461 - 27 Jan 2022
Cited by 37 | Viewed by 4824
Abstract
Exosomes are a class of small membrane-bound extracellular vesicles released by almost all cell types and present in all body fluids. Based on the studies of exosome content and their interactions with recipient cells, exosomes are now thought to mediate “targeted” information transfer. [...] Read more.
Exosomes are a class of small membrane-bound extracellular vesicles released by almost all cell types and present in all body fluids. Based on the studies of exosome content and their interactions with recipient cells, exosomes are now thought to mediate “targeted” information transfer. Tumor-derived exosomes (TEX) carry a cargo of molecules different from that of normal cell-derived exosomes. TEX functions to mediate distinct biological effects such as receptor discharge and intercellular cross-talk. The immune system defenses, which may initially restrict tumor progression, are progressively blunted by the broad array of TEX molecules that activate suppressive pathways in different immune cells. Herein, we provide a review of the latest research progress on TEX in the context of tumor-mediated immune suppression and discuss the potential as well as challenges of TEX as a target of immunotherapy. Full article
(This article belongs to the Special Issue Frontiers in Immuno-Oncology)
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