Prostate cancer and possibilities of immunotherapy

Abstract

The review focused on analysis of immunity disorders in prostate cancer and capabilities of immunotherapy for recovering the
immunity to destroy the tumor. The first part of the review analyzed the anticancer immune cycle and its regulators, CTLA-4 and
PD-1. This cycle consists of seven stages: 1) releasing tumor antigens; 2) capturing antigens; 3) antigen presentation and CTL
activation; 4) CTL transportation with blood flow to the tumor site; 5) CTL infiltration of the tumor; 6) CTL recognition of cancer
cells; and 7) destruction of cancer cells. Then the authors addressed the tumor capability for immunoediting the anticancer cycle
by 1) presentation of non-immunogenic antigens or apoptotic death without releasing antigens; 2) increasing production of
IDO, the anti-inflammatory cytokines, CTLA-4, PD-1, and PD-L1/PD-L2, and engaging MDSC, Tregs, and M2 macrophages to
disrupt the antigen presentation process and reduce the CTL activity and survival; 3) destruction of the chemokines, CX3CL1,
CXCL9, CXCL10, and CCL5 and release of VEGF to reduce CTL migration to the tumor; and 4) reducing the amount of MHCI to
restrict the CTL recognition of cancer cells. These mechanisms ensure the tumor survival during the immune attack. The following
technologies of anti-cancer immunotherapy were analyzed: 1) direct stimulation of anti-tumor immunity, for instance with
vaccines and CTL/TIL; 2) mimicking key stages of the anti-cancer cycle, for instance, using lymphocytes with modified TCR and
CAR-T cells; 3) inhibition of immunosuppression, for instance, with PD-1 and CTLA-4 inhibitors; and 4) combinations of two or
more of these technologies. Already now immunotherapy demonstrates its potentiality as a most effective anti-cancer treatment
largely due to using the patient’s own immunity. This gives rise to the hope that as immunotherapy is enhanced it will be able to
completely and safely destroy cancer.