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Clinical application of immune checkpoints in targeted immunotherapy of prostate cancer
Sevda Jafari1,2, Ommoleila Molavi3,4,5, Houman Kahroba6,7
1Biotechnology Research Center, Tabriz University of Medical Science, Tabriz, Iran.
Abstract:
Immunotherapy is considered as an effective method for cancer treatment owing to the induction of specific and long-lasting anti-cancer effects. Immunotherapeutic strategies have shown significant success in human malignancies, particularly in prostate cancer (PCa), a major global health issue regarding its high metastatic rates. In fact, the first cancer vaccine approved by FDA was Provenge, which has been successfully used for treatment of PCa. Despite the remarkable success of cancer immunotherapy in PCa, many of the developed immunotherapy methods show poor therapeutic outcomes. Immunosuppression in tumor microenvironment (TME) induced by non-functional T cells (CD4+ and CD8+), tolerogenic dendritic cells (DCs), and regulatory T cells, has been reported to be the main obstacle to the effectiveness of anti-tumor immune responses induced by an immunotherapy method. The present review particularly focuses on the latest findings of the immune checkpoints (ICPs), including CTLA-4, PD-1, PD-L1, LAG-3, OX40, B7-H3, 4-1BB, VISTA, TIM-3, and ICOS; these checkpoints are able to have immune modulatory effects on the TME of PCa. This paper further discusses different approaches in ICPs targeting therapy and summarizes the latest advances in the clinical application of ICP-targeted therapy as monotherapy or in combination with other cancer therapy modalities in PCa.
Insights
Immunotherapy shows promise for prostate cancer (PCa) treatment, but tumor microenvironment immunosuppression hinders effectiveness. Targeting immune checkpoints (ICPs) offers a new strategy to overcome these obstacles and improve anti-cancer responses.
Area of Science:
- Oncology
- Immunology
- Cancer Research
Background:
- Immunotherapy has demonstrated success in treating various cancers, including prostate cancer (PCa).
- Despite advancements, many immunotherapies for PCa yield suboptimal outcomes due to immunosuppression within the tumor microenvironment (TME).
- Key factors contributing to TME immunosuppression include non-functional T cells, tolerogenic dendritic cells, and regulatory T cells.
Purpose of the Study:
- To review the latest findings on immune checkpoints (ICPs) and their modulatory effects on the PCa TME.
- To discuss various ICP-targeting therapeutic approaches.
- To summarize recent clinical advancements in ICP-targeted therapies for PCa.
Main Methods:
- Literature review focusing on immune checkpoints (CTLA-4, PD-1, PD-L1, LAG-3, OX40, B7-H3, 4-1BB, VISTA, TIM-3, ICOS).
- Analysis of ICPs' roles in modulating the prostate cancer tumor microenvironment.
- Synthesis of data on clinical applications of ICP-targeted therapies.
Main Results:
- Identified several ICPs (CTLA-4, PD-1, PD-L1, etc.) that significantly influence the PCa TME.
- Discussed diverse strategies for targeting these ICPs.
- Summarized current clinical progress of ICP-targeted therapies, both as monotherapy and in combination treatments.
Conclusions:
- Immune checkpoints play a critical role in regulating anti-tumor immunity in prostate cancer.
- Targeting ICPs represents a promising therapeutic avenue for improving immunotherapy outcomes in PCa.
- Further research and clinical trials are essential to optimize ICP-targeted strategies for PCa treatment.
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