Synergistic Antitumor Effects and Pharmacological Interactions of Immune Checkpoint Inhibitors Combined with Chemotherapeutic Agents: Mechanisms and Clinical Translation

Keyi Yuan; Dingru Hong; Siyu Zhao; Shiyu Liu; Siqi Song

doi:10.18063/JMDS.v10i3.655

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26 September 2025

Synergistic Antitumor Effects and Pharmacological Interactions of Immune Checkpoint Inhibitors Combined with Chemotherapeutic Agents: Mechanisms and Clinical Translation

Keyi Yuan^1*, Dingru Hong², Siyu Zhao³, Shiyu Liu¹, Siqi Song¹

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¹ China Pharmaceutical University, School of Chinese Medicine, Nanjing 211198, Jiangsu, China

² China Pharmaceutical University, School of Clinical Pharmacy, Nanjing 211198, Jiangsu, China

³ China Pharmaceutical University, School of life science and technology, Nanjing 211198, Jiangsu, China

JMDS 2025 , 10(3), 63–70; https://doi.org/10.18063/JMDS.v10i3.655

© 2025 by the Author. Licensee Whioce Publishing, Singapore. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC BY-NC 4.0) ( https://creativecommons.org/licenses/by-nc/4.0/ )

Abstract

This paper provides a comprehensive literature review of the combination of immune checkpoint inhibitors (ICIs) and chemotherapy drugs in the field of synergistic antitumor therapy, aiming to summarize and analyze the current status, key issues, and future trends of tumor chemotherapy combined with immunotherapy. Research indicates that chemotherapy drugs enhance the immune system's ability to recognize and kill tumors by inducing immunogenic cell death (ICD) and altering the tumor microenvironment (TME). This paper provides a detailed analysis of drug metabolism enzymes and transporters, time-dependent interactions, dual pathways for immune system activation, intrinsic sensitization of tumor cells, the microbiome-immunotherapy axis, mechanisms of resistance and reversal strategies, as well as breakthroughs in novel delivery systems. Finally, this paper discusses improvements and prospects for future immunotherapy-chemotherapy combination studies. Personalized dosing and toxicity management remain major challenges, and future efforts should focus on optimizing treatment regimens using multi-omics data and organoid/PDX models.

Keywords

Immune checkpoint inhibitors

immunochemotherapy

synergistic antitumor effects

tumor microenvironment

novel delivery systems

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