AUTHOR=Opzoomer James W. , Sosnowska Dominika , Anstee Joanne E. , Spicer James F. , Arnold James N. TITLE=Cytotoxic Chemotherapy as an Immune Stimulus: A Molecular Perspective on Turning Up the Immunological Heat on Cancer JOURNAL=Frontiers in Immunology VOLUME=10 YEAR=2019 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.01654 DOI=10.3389/fimmu.2019.01654 ISSN=1664-3224 ABSTRACT=
Cytotoxic chemotherapeutics (CCTs) are widely used in the treatment of cancer. Although their mechanisms of action have been best understood in terms of targeting the apparatus of mitosis, an ability to stimulate anti-tumor immune responses is increasing the recognition of these agents as immunotherapies. Immune checkpoint blockade antibodies neutralize important, but specific, immune-regulatory interactions such as PD-1/PD-L1 and CTLA-4 to improve the anti-tumor immune response. However, CCTs can provide a broad-acting immune-stimulus against cancer, promoting both T-cell priming and recruitment to the tumor, which compliments the effects of immune checkpoint blockade. A key pathway in this process is “immunogenic cell death” (ICD) which occurs as a result of tumor cell endoplasmic reticulum stress and apoptosis elicited by CCTs. ICD involves a series of non-redundant signaling events which break tolerance and license anti-tumor antigen-specific T-cells, allowing CCTs to act as “