Cancer development is associated with a number of genetic and epigenetic alternations. Normally, these alterations are detected by the immune system in a process called immune surveillance, where cancer cell killing is mediated by cytotoxic T lymphocytes (CTL) and natural killer cells (NK cells). Yet, tumor progression and development indicate that cancer cells have acquired mechanisms to avoid immune destruction. Various immune evasion mechanisms have been reported before such as impaired antigen presentation and activation of CTL and NK cells, immunosuppression, and induction of tolerance. Although current treatment methods are shifting towards more targeted strategies in prostate cancer, such as immunotherapy, a better understanding of the cancer-immune interactions and immune evasion mechanisms is yet to be established.
More immunotherapies are being developed and approved by the FDA for treating cancer. In prostate cancer, Sipuleucel-T, an autologous cellular immunotherapy, was approved by FDA for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer. Intensive investigation on other immunotherapies is ongoing in prostate cancer. These include blockade of negative checkpoint regulators (PD-1, CTLA4) and Ig superfamily member V-domain Ig-containing suppressor of T-cell activation (VISTA), chimeric antigen receptor-modified T (CAR-T) cells against prostate lineage-unique proteins (PLUPs), and monoclonal antibodies targeting immunoinhibitory molecules. However, the optimal choice of treatment for a prostate cancer patient needs to target their specific mechanisms of immune evasion, which are poorly studied. In this study, we will use The Cancer Genome Atlas RNA-seq data to check for immune evasion gene expression in prostate cancer patients to identify at the different mechanisms by which cancer avoids immune destruction. We will use a sequential biclustering algorithm developed by our group, to group prostate cancer patients based on their similarities in immune evasion gene expression. A similar unpublished work was done by our group on breast cancer where we identified 7 different groups of patients, each with different mechanisms or combination of evasion mechanism. We also showed that triple negative breast cancer can be immunogenic and non-immunogenic. This group-based identification of evasion mechanisms will not only provide a better understanding of the different immune evasion mechanisms in prostate cancer, but will also shed light on potential combinations of mechanism. This in turn, will help guide the choice of single and combined immunotherapeutic approches.
Citation Format: Mayassa J. Bou-Dargham, Yuhang Liu, Qing-Xiang Amy Sang, Jinfeng Zhang. The different immune evasion mechanisms in human prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4046.