The tumor immune contexture of prostate cancer
- 1Queen's University, Canada
- 2Dalhousie University, Canada
One in seven men in North America is expected to be diagnosed with prostate cancer (PCa) during their lifetime1,2. While a wide range of treatment options including surgery, radiation, androgen ablation and chemotherapy have been in practice for the last few decades, there are limited treatment options for metastatic and treatment resistant disease. Immunotherapy targeting T-cell associated immune checkpoints such as CTLA-4, PD-L1 and PD-1 have not yet proven to be efficacious in PCa. Tumor mutational burden, mutations in DNA damage repair genes, immune cell composition and density in combination with their spatial organization, and expression of immune checkpoint proteins are some of the factors influencing the success of immune checkpoint inhibitor therapies. The paucity of these features in PCa potentially makes them unresponsive to contemporary immune checkpoint inhibition. In this review, we highlight the hallmark events in the PCa tumor immune microenvironment and provide insights into the current state of knowledge in this field with a focus on the role of tumor cell intrinsic events that potentially regulate immune related events and determine therapeutic outcomes. We surmise that the cumulative impact of factors such as the pre-treatment immune status, PTEN expression, DNA damage repair gene mutations, and the effects of conventionally used treatments on the anti-tumor immune response which should be considered in immunotherapy trial design in PCa.
Keywords: Tumor immune microenvironment, Immunotherapy, DNA damage response, PTEN (phosphatase and tensin homolog), prostate cancer
Received: 27 Dec 2018;
Accepted: 07 Mar 2019.
Edited by:Leila Akkari, The Netherlands Cancer Institute (NKI), Netherlands
Reviewed by:Zong Sheng Guo, School of Medicine, University of Pittsburgh, United States
Ekaterina Jordanova, Center for Gynaecologic Oncology Amsterdam, Netherlands
Copyright: © 2019 Vitkin, Nersesian, Siemens and Koti. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Dr. David R. Siemens, Queen's University, Kingston, K7L 3N6, Ontario, Canada, firstname.lastname@example.org
Dr. Madhuri Koti, Queen's University, Kingston, K7L 3N6, Ontario, Canada, email@example.com