期刊
FRONTIERS IN IMMUNOLOGY
卷 12, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.641307
关键词
dendritic cell; vaccine; prostate cancer; tumor; immune system; immunotherapy
类别
资金
- Cancer Institute New South Wales Translational Program Grant [11/TPG/3-02]
- Australian Postgraduate Award
- Sydney Catalyst Topup Scholarship
Despite the success of using checkpoint inhibitors to reprim T cells to recognize tumors in certain malignancies, including melanoma, lung, and renal cell carcinoma, many tumors, such as prostate cancer, remain resistant to such treatment. DC-based immunotherapy, such as Sipuleucel-T, has shown improved overall survival in prostate cancer, but further research into DC vaccines has been limited. Understanding the immunosuppressive environment of prostate cancer and developing new vaccine strategies that can overcome this environment is essential for future success in immunotherapy.
Tumors evade the immune system though a myriad of mechanisms. Using checkpoint inhibitors to help reprime T cells to recognize tumor has had great success in malignancies including melanoma, lung, and renal cell carcinoma. Many tumors including prostate cancer are resistant to such treatment. However, Sipuleucel-T, a dendritic cell (DC) based immunotherapy, improved overall survival (OS) in prostate cancer. Despite this initial success, further DC vaccines have failed to progress and there has been limited uptake of Sipuleucel-T in the clinic. We know in prostate cancer (PCa) that both the adaptive and the innate arms of the immune system contribute to the immunosuppressive environment. This is at least in part due to dysfunction of DC that play a crucial role in the initiation of an immune response. We also know that there is a paucity of DC in PCa, and that those there are immature, creating a tolerogenic environment. These attributes make PCa a good candidate for a DC based immunotherapy. Ultimately, the knowledge gained by much research into antigen processing and presentation needs to translate from bench to bedside. In this review we will analyze why newer vaccine strategies using monocyte derived DC (MoDC) have failed to deliver clinical benefit, particularly in PCa, and highlight the emerging antigen loading and presentation technologies such as nanoparticles, antibody-antigen conjugates and virus co-delivery systems that can be used to improve efficacy. Lastly, we will assess combination strategies that can help overcome the immunosuppressive microenvironment of PCa.
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