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10 pages, 1638 KiB

Open AccessArticle

Phenotype and Reactivity of Lymphocytes Expanded from Benign Prostate Hyperplasic Tissues and Prostate Cancer

by Ritaparna Ahmed, Leyder Elena Lozano, Amandine Anastasio, Sebastien Lofek, Beatris Mastelic-Gavillet, Blanca Navarro Rodrigo, Sylvain Nguyen, Florence Dartiguenave, Sonia-Cristina Rodrigues-Dias, Valérie Cesson, Massimo Valério, Beat Roth, Lana Elias Kandalaft, Irina Redchenko, Adrian Vivian Sinton Hill, Alexandre Harari, Pedro Romero, Laurent Derré and Selena Viganó

Cancers 2023, 15(12), 3114; https://doi.org/10.3390/cancers15123114 - 8 Jun 2023

Viewed by 1695

Abstract

Benign prostate hyperplasia (BPH) is a frequent condition in aging men, which affects life quality, causing principally lower urinary tract symptoms. Epidemiologic studies suggest that BPH may raise the risk of developing prostate cancer (PCa), most likely promoting a chronic inflammatory environment. Studies [...] Read more.

Benign prostate hyperplasia (BPH) is a frequent condition in aging men, which affects life quality, causing principally lower urinary tract symptoms. Epidemiologic studies suggest that BPH may raise the risk of developing prostate cancer (PCa), most likely promoting a chronic inflammatory environment. Studies aiming at elucidating the link and risk factors that connect BPH and PCa are urgently needed to develop prevention strategies. The BPH microenvironment, similar to the PCa one, increases immune infiltration of the prostate, but, in contrast to PCa, immunosuppression may not be established yet. In this study, we found that prostate-infiltrating lymphocytes (PILs) expanded from hyperplastic prostate tissue recognized tumor-associated antigens (TAA) and autologous tissue, regardless of the presence of tumor cells. PILs expanded from BPH samples of patients with PCa, however, seem to respond more strongly to autologous tissue. Phenotypic characterization of the infiltrating PILs revealed a trend towards better expanding CD4⁺ T cells in infiltrates derived from PCa, but no significant differences were found. These findings suggest that T cell tolerance is compromised in BPH-affected prostates, likely due to qualitative or quantitative alterations of the antigenic landscape. Our data support the hypothesis that BPH increases the risk of PCa and may pave the way for new personalized preventive vaccine strategies for these patients. Full article

(This article belongs to the Special Issue Advances in Immunotherapy for Genitourinary Malignancies)

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14 pages, 1320 KiB

Open AccessArticle

The Association between a Decrease in On-Treatment Neutrophil-to-Eosinophil Ratio (NER) at Week 6 after Ipilimumab Plus Nivolumab Initiation and Improved Clinical Outcomes in Metastatic Renal Cell Carcinoma

by Yu-Wei Chen, Matthew D. Tucker, Landon C. Brown, Hesham A. Yasin, Kristin K. Ancell, Andrew J. Armstrong, Kathryn E. Beckermann, Nancy B. Davis, Michael R. Harrison, Elizabeth G. Kaiser, Renee K. McAlister, Kerry R. Schaffer, Deborah E. Wallace, Daniel J. George, W. Kimryn Rathmell, Brian I. Rini and Tian Zhang

Cancers 2022, 14(15), 3830; https://doi.org/10.3390/cancers14153830 - 7 Aug 2022

Cited by 10 | Viewed by 3362

Abstract

A lower baseline neutrophil-to-eosinophil ratio (NER) has been associated with improved responses to immune checkpoint inhibitors (ICI)-treated metastatic renal cell carcinoma (mRCC). This study investigated the decrease in NER at week 6 after ipilimumab/nivolumab (ipi/nivo) initiation and treatment responses in mRCC. A retrospective [...] Read more.

A lower baseline neutrophil-to-eosinophil ratio (NER) has been associated with improved responses to immune checkpoint inhibitors (ICI)-treated metastatic renal cell carcinoma (mRCC). This study investigated the decrease in NER at week 6 after ipilimumab/nivolumab (ipi/nivo) initiation and treatment responses in mRCC. A retrospective study of ipi/nivo-treated mRCC at two US academic cancer centers was conducted. A landmark analysis at week 6 was performed to assess the association between the change in NER and clinical responses (progression-free survival (PFS)/overall survival (OS)). Week 6 NER was modeled as a continuous variable, after log transformation (Ln NER), and a categorical variable by percent change. There were 150 mRCC patients included: 78% had clear cell histology, and 78% were IMDC intermediate/poor risk. In multivariable regression analysis, every decrease of 1 unit of Ln NER at week 6 was associated with improved PFS (adjusted hazard ratio (AHR): 0.78, p-value:0.005) and OS (AHR: 0.67, p-value: 0.002). When NER was modeled by percent change, decreased NER > 50% was associated with improved PFS (AHR: 0.55, p-value: 0.03) and OS (AHR: 0.37, p-value: 0.02). The decrease in week 6 NER was associated with improved PFS/OS in ipi/nivo-treated mRCC. Prospective studies are warranted to validate NER change as a biomarker to predict ICI responses. Full article

(This article belongs to the Special Issue Advances in Immunotherapy for Genitourinary Malignancies)

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16 pages, 4274 KiB

Open AccessArticle

Single-Cell Analyses of a Novel Mouse Urothelial Carcinoma Model Reveal a Role of Tumor-Associated Macrophages in Response to Anti-PD-1 Therapy

by Dongbo Xu, Li Wang, Kyle Wieczorek, Yali Zhang, Zinian Wang, Jianmin Wang, Bo Xu, Prashant K. Singh, Yanqing Wang, Xiaojing Zhang, Yue Wu, Gary J. Smith, Kristopher Attwood, Yuesheng Zhang, David W. Goodrich and Qiang Li

Cancers 2022, 14(10), 2511; https://doi.org/10.3390/cancers14102511 - 19 May 2022

Cited by 4 | Viewed by 3972

Abstract

Approximately 80% of patients with advanced bladder cancer do not respond to immune checkpoint inhibitor (ICI) immunotherapy. Therefore, there is an urgent unmet need to develop clinically relevant preclinical models so that factors governing immunotherapy responses can be studied in immunocompetent mice. We [...] Read more.

Approximately 80% of patients with advanced bladder cancer do not respond to immune checkpoint inhibitor (ICI) immunotherapy. Therefore, there is an urgent unmet need to develop clinically relevant preclinical models so that factors governing immunotherapy responses can be studied in immunocompetent mice. We developed a line of mouse triple knockout (TKO: Trp53, Pten, Rb1) urothelial carcinoma organoids transplanted into immunocompetent mice. These bladder tumors recapitulate the molecular phenotypes and heterogeneous immunotherapy responses observed in human bladder cancers. The TKO organoids were characterized in vivo and in vitro and compared to the widely used MB49 murine bladder cancer model. RNAseq analysis of the TKO tumors demonstrated a basal subtype. The TKO xenografts demonstrated the expression of urothelial markers (CK5, CK7, GATA3, and p63), whereas MB49 subcutaneous xenografts did not express urothelial markers. Anti-PD-1 immunotherapy resulted in a mixed pattern of treatment responses for individual tumors. Eight immune cell types were identified (basophils, B cells, dendritic cells, macrophages, monocytes, neutrophils, NK cells, and T cells) in ICI-treated xenografts. Responder xenografts displayed significantly increased immune cell infiltration (15.3%, 742 immune cells/4861 total cells) compared to the non-responder tumors (10.1%, 452 immune cells/4459 total cells, Fisher Exact Test p < 0.0001). Specifically, there were more T cells (1.0% vs. 0.4%, p = 0.002) and macrophages (8.6% vs. 6.4%, p = 0.0002) in responder xenografts than in non-responder xenografts. In conclusion, we have developed a novel preclinical model that exhibits a mixed pattern of response to anti-PD-1 immunotherapy. The higher percentage of macrophage tumor infiltration in responders suggests a potential role for the innate immune microenvironment in regulating ICI treatment responses. Full article

(This article belongs to the Special Issue Advances in Immunotherapy for Genitourinary Malignancies)

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16 pages, 3112 KiB

Open AccessArticle

Geospatial Cellular Distribution of Cancer-Associated Fibroblasts Significantly Impacts Clinical Outcomes in Metastatic Clear Cell Renal Cell Carcinoma

by Nicholas H. Chakiryan, Gregory J. Kimmel, Youngchul Kim, Joseph O. Johnson, Noel Clark, Ali Hajiran, Andrew Chang, Ahmet M. Aydin, Logan Zemp, Esther Katende, Jad Chahoud, Meghan C. Ferrall-Fairbanks, Philippe E. Spiess, Natasha Francis, Michelle Fournier, Jasreman Dhillon, Jong Y. Park, Liang Wang, James J. Mulé, Philipp M. Altrock and Brandon J. Manley Show full author list Hide full author list

Cancers 2021, 13(15), 3743; https://doi.org/10.3390/cancers13153743 - 26 Jul 2021

Cited by 13 | Viewed by 3404

Abstract

Cancer-associated fibroblasts (CAF) are highly prevalent cells in the tumor microenvironment in clear cell renal cell carcinoma (ccRCC). CAFs exhibit a pro-tumor effect in vitro and have been implicated in tumor cell proliferation, metastasis, and treatment resistance. Our objective is to analyze the [...] Read more.

Cancer-associated fibroblasts (CAF) are highly prevalent cells in the tumor microenvironment in clear cell renal cell carcinoma (ccRCC). CAFs exhibit a pro-tumor effect in vitro and have been implicated in tumor cell proliferation, metastasis, and treatment resistance. Our objective is to analyze the geospatial distribution of CAFs with proliferating and apoptotic tumor cells in the ccRCC tumor microenvironment and determine associations with survival and systemic treatment. Pre-treatment primary tumor samples were collected from 96 patients with metastatic ccRCC. Three adjacent slices were obtained from 2 tumor-core regions of interest (ROI) per patient, and immunohistochemistry (IHC) staining was performed for αSMA, Ki-67, and caspase-3 to detect CAFs, proliferating cells, and apoptotic cells, respectively. H-scores and cellular density were generated for each marker. ROIs were aligned, and spatial point patterns were generated, which were then used to perform spatial analyses using a normalized Ripley’s K function at a radius of 25 μm (nK(25)). The survival analyses used an optimal cut-point method, maximizing the log-rank statistic, to stratify the IHC-derived metrics into high and low groups. Multivariable Cox regression analyses were performed accounting for age and International Metastatic RCC Database Consortium (IMDC) risk category. Survival outcomes included overall survival (OS) from the date of diagnosis, OS from the date of immunotherapy initiation (OS-IT), and OS from the date of targeted therapy initiation (OS-TT). Therapy resistance was defined as progression-free survival (PFS) <6 months, and therapy response was defined as PFS >9 months. CAFs exhibited higher cellular clustering with Ki-67⁺ cells than with caspase-3⁺ cells (nK(25): Ki-67 1.19; caspase-3 1.05; p = 0.04). The median nearest neighbor (NN) distance from CAFs to Ki-67⁺ cells was shorter compared to caspase-3⁺ cells (15 μm vs. 37 μm, respectively; p < 0.001). Multivariable Cox regression analyses demonstrated that both high Ki-67⁺ density and H-score were associated with worse OS, OS-IT, and OS-TT. Regarding αSMA+CAFs, only a high H-score was associated with worse OS, OS-IT, and OS-TT. For caspase-3⁺, high H-score and density were associated with worse OS and OS-TT. Patients whose tumors were resistant to targeted therapy (TT) had higher Ki-67 density and H-scores than those who had TT responses. Overall, this ex vivo geospatial analysis of CAF distribution suggests that close proximity clustering of tumor cells and CAFs potentiates tumor cell proliferation, resulting in worse OS and resistance to TT in metastatic ccRCC. Full article

(This article belongs to the Special Issue Advances in Immunotherapy for Genitourinary Malignancies)

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20 pages, 19673 KiB

Open AccessArticle

Immune Checkpoints Inhibitors and Chemotherapy as First-Line Treatment for Metastatic Urothelial Carcinoma: A Network Meta-Analysis of Randomized Phase III Clinical Trials

by Hsiao-Ling Chen, Vinson Wai-Shun Chan, Yu-Kang Tu, Erica On-Ting Chan, Hsiu-Mei Chang, Yung-Shun Juan, Jeremy Yuen-Chun Teoh and Hsiang Ying Lee

Cancers 2021, 13(6), 1484; https://doi.org/10.3390/cancers13061484 - 23 Mar 2021

Cited by 5 | Viewed by 2867

Abstract

Immune checkpoints inhibitors (ICIs) were considered as second-line treatments in metastatic urothelial carcinoma (mUC) based on better survival benefit and safety profile than chemotherapy (CTX). We aimed to assess different ICIs regimens in the efficacy and safety for front-line treatments in mUC patients. [...] Read more.

Immune checkpoints inhibitors (ICIs) were considered as second-line treatments in metastatic urothelial carcinoma (mUC) based on better survival benefit and safety profile than chemotherapy (CTX). We aimed to assess different ICIs regimens in the efficacy and safety for front-line treatments in mUC patients. A comprehensive literature search was performed and Phase II-III randomized controlled trials (RCTs) on ICIs for patients with mUC were included. The outcome was evaluated by overall survival (OS), progression of free survival (PFS), objective response rate (ORR), and grade 3–5 adverse events. Network meta-analysis was used to estimate the effect size. Surface under cumulative ranking curves (SUCRAs) were applied to rank the included treatments for each outcome. Results: The survival benefit of a single ICI was non-inferiority to chemotherapy (CTX). Although no superior effects were indicated, combination therapy (either ICIs plus CTX or ICIs plus ICIs) presented better OS compared with CTX alone. In terms of PFS, combination therapy produced a noticeable benefit over CTX. Regarding the SUCRA ranking, atezolizumab plus CTX was associated with the best ranking for OS and pembrolizumab plus CTX was the best in PFS. In terms of safety, a single ICI had better safety profile than CTX and combination therapy had a similar risk of grade 3–5 adverse events with CTX. Conclusions: Our NMA results revealed that combination therapy has better ranking compared with monotherapy in OS and acceptable AEs. ICIs alone present non-inferior OS but a lower incidence of AEs compared with CTX. Full article

(This article belongs to the Special Issue Advances in Immunotherapy for Genitourinary Malignancies)

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Review

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13 pages, 1345 KiB

Open AccessReview

Roles of Androgen Receptor Signaling in Urothelial Carcinoma

by Debasish Sundi, Katharine A. Collier, Yuanquan Yang, Dayssy Alexandra Diaz, Kamal S. Pohar, Eric A. Singer, Sanjay Gupta, William E. Carson III, Steven K. Clinton, Zihai Li and Edward M. Messing

Cancers 2024, 16(4), 746; https://doi.org/10.3390/cancers16040746 - 10 Feb 2024

Cited by 1 | Viewed by 1788

Abstract

Preclinical and clinical data suggest that androgen receptor signaling strongly contributes to bladder cancer development. The roles of the androgen receptor in bladder carcinogenesis have obvious implications for understanding the strong male sex bias in this disease and for potential therapeutic strategies as [...] Read more.

Preclinical and clinical data suggest that androgen receptor signaling strongly contributes to bladder cancer development. The roles of the androgen receptor in bladder carcinogenesis have obvious implications for understanding the strong male sex bias in this disease and for potential therapeutic strategies as well. In this review, we summarize what is known about androgen receptor signaling in urothelial carcinoma as well as in tumor-infiltrating immune cells, reviewing preclinical and clinical data. We also highlight clinical trial efforts in this area. Full article

(This article belongs to the Special Issue Advances in Immunotherapy for Genitourinary Malignancies)

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11 pages, 288 KiB

Open AccessReview

The Current and Future Promises of Combination Radiation and Immunotherapy for Genitourinary Cancers

by Ava Saidian, Isabella Dolendo, Andrew Sharabi, Tyler F. Stewart, Brent Rose, Rana R. McKay, Aditya Bagrodia and Amirali Salmasi

Cancers 2023, 15(1), 127; https://doi.org/10.3390/cancers15010127 - 25 Dec 2022

Cited by 4 | Viewed by 2192

Abstract

As the indications for the use of immunotherapy in genitourinary malignancies expand, its role in combination with standard or conventional therapies has become the subject of contemporary studies. Radiotherapy has multiple immunomodulating effects on anti-tumor immune response, which highlights potential synergistic role with [...] Read more.

As the indications for the use of immunotherapy in genitourinary malignancies expand, its role in combination with standard or conventional therapies has become the subject of contemporary studies. Radiotherapy has multiple immunomodulating effects on anti-tumor immune response, which highlights potential synergistic role with immunotherapy agents. We sought to review the body of published data studying the combination of immunotherapy and radiotherapy as well as the rationale for combination therapy. Trial information and primary articles were obtained using the following terms “immunotherapy”, “radiotherapy”, “prostate cancer”, and “bladder cancer.” All articles and trials were screened to ensure they included combination radiotherapy and immunotherapy. The effects of radiation on the immune system, including both immunogenic and immunosuppressive effects, have been reported. There is a potential for combinatorial or synergistic effects between radiation therapy and immunotherapy in treating bladder and prostate cancers. However, results from ongoing and future clinical trials are needed to best integrate immunotherapy into current standard of care treatments for GU cancers. Full article

(This article belongs to the Special Issue Advances in Immunotherapy for Genitourinary Malignancies)

14 pages, 814 KiB

Open AccessEditor’s ChoiceReview

Immune Checkpoint Inhibitors as a Neoadjuvant/Adjuvant Treatment of Muscle-Invasive Bladder Cancer: A Systematic Review

by Biagio Barone, Armando Calogero, Luca Scafuri, Matteo Ferro, Giuseppe Lucarelli, Erika Di Zazzo, Enrico Sicignano, Alfonso Falcone, Lorenzo Romano, Luigi De Luca, Francesco Oliva, Benito Fabio Mirto, Federico Capone, Ciro Imbimbo and Felice Crocetto

Cancers 2022, 14(10), 2545; https://doi.org/10.3390/cancers14102545 - 21 May 2022

Cited by 44 | Viewed by 4223

Abstract

Bladder cancer is the ninth most common cancer worldwide. Over 75% of non-muscle invasive cancer patients require conservative local treatment, while the remaining 25% of patients undergo radical cystectomy or radiotherapy. Immune checkpoint inhibitors represent a novel class of immunotherapy drugs that restore [...] Read more.

Bladder cancer is the ninth most common cancer worldwide. Over 75% of non-muscle invasive cancer patients require conservative local treatment, while the remaining 25% of patients undergo radical cystectomy or radiotherapy. Immune checkpoint inhibitors represent a novel class of immunotherapy drugs that restore natural antitumoral immune activity via the blockage of inhibitory receptors and ligands expressed on antigen-presenting cells, T lymphocytes and tumour cells. The use of immune checkpoint inhibitors in bladder cancer has been expanded from the neoadjuvant setting, i.e., after radical cystectomy, to the adjuvant setting, i.e., before the operative time or chemotherapy, in order to improve the overall survival and to reduce the morbidity and mortality of both the disease and its treatment. However, some patients do not respond to checkpoint inhibitors. As result, the capability for identifying patients that are eligible for this immunotherapy represent one of the efforts of ongoing studies. The aim of this systematic review is to summarize the most recent evidence regarding the use of immune checkpoint inhibitors, in a neoadjuvant and adjuvant setting, in the treatment of muscle-invasive bladder cancer. Full article

(This article belongs to the Special Issue Advances in Immunotherapy for Genitourinary Malignancies)

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13 pages, 661 KiB

Open AccessReview

Cost-Effectiveness of Immune Checkpoint Inhibitors in Urothelial Carcinoma—A Review

by Arman S. Walia, Randy F. Sweis, Piyush K. Agarwal, Andrew K. Kader and Parth K. Modi

Cancers 2022, 14(1), 73; https://doi.org/10.3390/cancers14010073 - 24 Dec 2021

Cited by 4 | Viewed by 3043

Abstract

Over the last decade, an increasing number of immune checkpoint inhibitors (ICIs) have been assessed for therapeutic efficacy in urothelial carcinoma (UC). The high cost has prompted multiple cost-effectiveness analyses for the various disease stages, with no established consensus. We reviewed the literature [...] Read more.

Over the last decade, an increasing number of immune checkpoint inhibitors (ICIs) have been assessed for therapeutic efficacy in urothelial carcinoma (UC). The high cost has prompted multiple cost-effectiveness analyses for the various disease stages, with no established consensus. We reviewed the literature to assess the available cost-effectiveness studies and summarize their findings. Studies were filtered for a calculated incremental cost-effectiveness ratio (ICER) to standardize comparison. Over 2600 articles were narrowed to eight primary investigations: one for BCG-refractory non-muscle invasive (NMI), one for neoadjuvant therapy in muscle-invasive (MI), and six for advanced disease. Cost-effectiveness was not achieved for NMI disease. Atezolizumab met the willingness-to-pay (WTP) threshold as neoadjuvant therapy for MI disease compared to chemotherapy, but with multiple limitations on the interpretation. Of the six studies on advanced disease, the results were mixed. This was at least partially attributable to varied methodologies including extrapolated time horizons, inconsistent cost inputs, and different WTP thresholds. Overall, the aggregate results were not compelling enough to establish ICIs as cost-effective compared to conventional chemotherapy. Value may improve with continued investigation into long-term outcomes, refined patient selection, and pricing discounts. Full article

(This article belongs to the Special Issue Advances in Immunotherapy for Genitourinary Malignancies)

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14 pages, 2013 KiB

Open AccessReview

Advances in Immunotherapy and the TGF-β Resistance Pathway in Metastatic Bladder Cancer

by David J. Benjamin and Yung Lyou

Cancers 2021, 13(22), 5724; https://doi.org/10.3390/cancers13225724 - 16 Nov 2021

Cited by 14 | Viewed by 4243

Abstract

Bladder cancer accounts for nearly 200,000 deaths worldwide yearly. Urothelial carcinoma (UC) accounts for nearly 90% of cases of bladder cancer. Cisplatin-based chemotherapy has remained the mainstay of treatment in the first-line setting for locally advanced or metastatic UC. More recently, the treatment [...] Read more.

Bladder cancer accounts for nearly 200,000 deaths worldwide yearly. Urothelial carcinoma (UC) accounts for nearly 90% of cases of bladder cancer. Cisplatin-based chemotherapy has remained the mainstay of treatment in the first-line setting for locally advanced or metastatic UC. More recently, the treatment paradigm in the second-line setting was drastically altered with the approval of several immune checkpoint inhibitors (ICIs). Given that only a small subset of patients respond to ICI, further studies have been undertaken to understand potential resistance mechanisms to ICI. One potential resistance mechanism that has been identified in the setting of metastatic UC is the TGF-β signaling pathway. Several pre-clinical and ongoing clinical trials in multiple advanced tumor types have evaluated several therapies that target the TGF-β pathway. In addition, there are ongoing and planned clinical trials combining TGF-β inhibition with ICI, which may provide a promising therapeutic approach for patients with advanced and metastatic UC. Full article

(This article belongs to the Special Issue Advances in Immunotherapy for Genitourinary Malignancies)

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16 pages, 1504 KiB

Open AccessReview

Overcoming Immune Resistance in Prostate Cancer: Challenges and Advances

by Miyad Movassaghi, Rainjade Chung, Christopher B. Anderson, Mark Stein, Yvonne Saenger and Izak Faiena

Cancers 2021, 13(19), 4757; https://doi.org/10.3390/cancers13194757 - 23 Sep 2021

Cited by 12 | Viewed by 3759

Abstract

The use of immunotherapy has become a critical treatment modality in many advanced cancers. However, immunotherapy in prostate cancer has not been met with similar success. Multiple interrelated mechanisms, such as low tumor mutational burden, immunosuppressive cells, and impaired cellular immunity, appear to [...] Read more.

The use of immunotherapy has become a critical treatment modality in many advanced cancers. However, immunotherapy in prostate cancer has not been met with similar success. Multiple interrelated mechanisms, such as low tumor mutational burden, immunosuppressive cells, and impaired cellular immunity, appear to subvert the immune system, creating an immunosuppressive tumor microenvironment and leading to lower treatment efficacy in advanced prostate cancer. The lethality of metastatic castrate-resistant prostate cancer is driven by the lack of therapeutic regimens capable of generating durable responses. Multiple strategies are currently being tested to overcome immune resistance including combining various classes of treatment modalities. Several completed and ongoing trials have shown that combining vaccines or checkpoint inhibitors with hormonal therapy, radiotherapy, antibody–drug conjugates, chimeric antigen receptor T cell therapy, or chemotherapy may enhance immune responses and induce long-lasting clinical responses without significant toxicity. Here, we review the current state of immunotherapy for prostate cancer, as well as tumor-specific mechanisms underlying therapeutic resistance, with a comprehensive look at the current preclinical and clinical immunotherapeutic strategies aimed at overcoming the immunosuppressive tumor microenvironment and impaired cellular immunity that have largely limited the utility of immunotherapy in advanced prostate cancer. Full article

(This article belongs to the Special Issue Advances in Immunotherapy for Genitourinary Malignancies)

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17 pages, 830 KiB

Open AccessReview

Clearing up Clear Cell: Clarifying the Immuno-Oncology Treatment Landscape for Metastatic Clear Cell RCC

by Sai Krishnaraya Doppalapudi, Zev R. Leopold, Akshay Thaper, Alain Kaldany, Kevin Chua, Hiren V. Patel, Arnav Srivastava and Eric A. Singer

Cancers 2021, 13(16), 4140; https://doi.org/10.3390/cancers13164140 - 17 Aug 2021

Cited by 12 | Viewed by 3067

Abstract

Patients with advanced or malignant renal cell carcinoma at the time of diagnosis have historically had a poor prognosis. Immunonologic agents have significantly altered the therapeutic landscape and clinical outcomes of these patients. In this review, we highlight recent and upcoming clinical trials [...] Read more.

Patients with advanced or malignant renal cell carcinoma at the time of diagnosis have historically had a poor prognosis. Immunonologic agents have significantly altered the therapeutic landscape and clinical outcomes of these patients. In this review, we highlight recent and upcoming clinical trials investigating the role of immunotherapies in clear cell RCC. In particular, we emphasize immunotherapy-based combinations, including immune checkpoint inhibitor (ICI) combinations, neoadjuvant, and adjuvant ICI, and ICI agents combined with anti-VEGF therapy. Full article

(This article belongs to the Special Issue Advances in Immunotherapy for Genitourinary Malignancies)

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