Overcoming Immune Resistance in Prostate Cancer: Challenges and Advances
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,...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-09-01
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| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/13/19/4757 |
| _version_ | 1797516744402665472 |
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| author | Miyad Movassaghi Rainjade Chung Christopher B. Anderson Mark Stein Yvonne Saenger Izak Faiena |
| author_facet | Miyad Movassaghi Rainjade Chung Christopher B. Anderson Mark Stein Yvonne Saenger Izak Faiena |
| author_sort | Miyad Movassaghi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T07:06:02Z |
| format | Article |
| id | doaj.art-bf410bc6448f499c91d11ba751d18cc6 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T07:06:02Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-bf410bc6448f499c91d11ba751d18cc62023-11-22T15:51:55ZengMDPI AGCancers2072-66942021-09-011319475710.3390/cancers13194757Overcoming Immune Resistance in Prostate Cancer: Challenges and AdvancesMiyad Movassaghi0Rainjade Chung1Christopher B. Anderson2Mark Stein3Yvonne Saenger4Izak Faiena5Department of Urology, Columbia University Irving Medical Center, New York, NY 10032, USADepartment of Urology, Columbia University Irving Medical Center, New York, NY 10032, USADepartment of Urology, Columbia University Irving Medical Center, New York, NY 10032, USADepartment of Medicine, Division of Medical Oncology, Columbia University Irving Medical Center, New York, NY 10032, USADepartment of Medicine, Division of Medical Oncology, Columbia University Irving Medical Center, New York, NY 10032, USADepartment of Urology, Columbia University Irving Medical Center, New York, NY 10032, USAThe 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.https://www.mdpi.com/2072-6694/13/19/4757immunotherapymetastatic castration resistant prostate cancertumor microenvironmentimmune resistancecombination therapiesimmune checkpoint inhibitors |
| spellingShingle | Miyad Movassaghi Rainjade Chung Christopher B. Anderson Mark Stein Yvonne Saenger Izak Faiena Overcoming Immune Resistance in Prostate Cancer: Challenges and Advances Cancers immunotherapy metastatic castration resistant prostate cancer tumor microenvironment immune resistance combination therapies immune checkpoint inhibitors |
| title | Overcoming Immune Resistance in Prostate Cancer: Challenges and Advances |
| title_full | Overcoming Immune Resistance in Prostate Cancer: Challenges and Advances |
| title_fullStr | Overcoming Immune Resistance in Prostate Cancer: Challenges and Advances |
| title_full_unstemmed | Overcoming Immune Resistance in Prostate Cancer: Challenges and Advances |
| title_short | Overcoming Immune Resistance in Prostate Cancer: Challenges and Advances |
| title_sort | overcoming immune resistance in prostate cancer challenges and advances |
| topic | immunotherapy metastatic castration resistant prostate cancer tumor microenvironment immune resistance combination therapies immune checkpoint inhibitors |
| url | https://www.mdpi.com/2072-6694/13/19/4757 |
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