[Mechanistic Basis and Clinical Significance of Cytotoxic Anticancer Drugs in Combination Immunotherapy].

Cytotoxic anticancer drugs, including alkylating agents or platinum‒based compounds, have been central to cancer treatment since the 1980s and remain in use today. Recently, following the emergence of immune checkpoint inhibitors(ICI)across multiple cancer types, attention has shifted to the potential of cytotoxic anticancer drugs to enhance cancer immunotherapy efficacy through immunogenic cell death. Furthermore, it has been suggested that these drugs can positively or negatively influence the anticancer immune response by acting on cell populations within the tumor microenvironment, such as Tregs, MDSCs, and macrophages, or by affecting systemic physiological changes, including the gut microbiota. While the combination therapy with cytotoxic anticancer drugs with ICIs had broadened treatment options for cancers with limited response to ICI monotherapy, the significance of such combination therapy may differ in cancers that respond well to ICI alone, such as in non‒small cell lung cancer with PD‒L1 high. This review discusses the clinical significance of cytotoxic anticancer drugs in combination immunotherapy, based on preclinical evidence and clinical trial results.