Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8536823 | Pharmacology & Therapeutics | 2018 | 8 Pages |
Abstract
Antitumor immunity relies on the ability of the immune system to recognize tumor cells as foreign and eliminate them. An effective immune response in this setting is due to surveillance of tumor-specific antigens that induce an adaptive immune response resulting in T-cell mediated cytotoxicity. Immune checkpoint inhibitors, specifically those targeting the programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) axis, have demonstrated promising activity in non-small cell lung cancer (NSCLC). However, there remains a crucial need for better treatment strategies for the majority of patients with advanced NSCLC, particularly in the frontline setting. Chemotherapy can increase antigenicity via immunogenic cell death (ICD) of tumor cells as well as also reduce “off target” immunosuppression in the tumor microenvironment (TME). Combining chemotherapy with PD-1 blockade harnesses the potential synergy between these agents and has led to encouraging results in the up-front treatment of NSCLC. In this review, we summarize the preclinical rationale behind these combinations and review recent trial data demonstrating their efficacy.
Keywords
ORRCTLA-4cytotoxic T-lymphocyte antigen-4TMEPD-1CrtPD-L1PFsadverse effectprogression-free survivaloverall survivalNSCLCNon-small cell lung cancerDendritic cellChemoradiotherapyProgrammed death ligand-1Immunogenic cell deathProgrammed cell death-1Immune checkpoint inhibitorsTumor microenvironmentobjective response rate
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Authors
Matthen Mathew, Thomas Enzler, Catherine A. Shu, Naiyer A. Rizvi,