Chemoimmunotherapy synergism: mechanisms and clinical applications

Abstract

Chemoimmunotherapy, combining chemotherapy and immunotherapy, has emerged as a promising strategy for treating various cancers. This approach leverages the complementary mechanisms of both modalities to enhance tumor eradication. Recent advances have shed new light on the synergistic interactions between chemotherapy and immunotherapy, revealing complex mechanisms that contribute to improved clinical outcomes. Chemotherapy induces immunogenic cell death, releasing tumor antigens and damage-associated molecular patterns (DAMPs) that stimulate immune responses. It also modulates the tumor microenvironment, enhancing immune cell infiltration and reducing immunosuppressive elements. Concurrently, immunotherapy, particularly immune checkpoint inhibitors, activates the immune system to more effectively target and destroy cancer cells. Clinical evidence demonstrates significant benefits of chemoimmunotherapy in various cancers, including non-small-cell lung cancer, triple-negative breast cancer, and melanoma. Recent trials, such as KEYNOTE- 189 and IMpassion130, have shown improved overall survival and progression-free survival compared to chemotherapy alone. Emerging biomarkers, including tumor mutational burden, Programmed Death Ligand- 1 (PD-L1) expression, and immune cell infiltration patterns, are refining patient selection and response prediction. Novel strategies, such as nanoparticle-based drug delivery systems and personalized medicine approaches, are being explored to optimize chemoimmunotherapy combinations. However, challenges remain, including managing treatment-related toxicities, determining optimal dosing and sequencing, and addressing potential resistance mechanisms. Ongoing research focuses on elucidating the complex interplay between chemotherapy-induced immunomodulation and immune checkpoint inhibition to further improve treatment efficacy and patient outcomes. This review provides a comprehensive update on the mechanisms, clinical applications, and future directions of chemoimmunotherapy, highlighting its potential to revolutionize cancer treatment strategies. Clinical trial number: not applicable.

Keywords: Chemoimmunotherapy; Immune checkpoint inhibitors; Malignancy; Melanoma; Synergism.