Open Access

REVIEW

Unraveling Immunotherapy Resistance in Solid Tumors: Decoding Mechanisms and Charting Future Therapeutic Landscapes

Huan Wang^1,#, Jindong Xie^1,#, Na Li¹, Qianwen Liu¹, Wenqi Song¹, Wenkuan Chen¹, Cheng Peng^2,*, Hailin Tang^1,*

1 State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China
2 State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China

* Corresponding Authors: Cheng Peng. Email: ; Hailin Tang. Email:
# Huan Wang and Jindong Xie contributed equally to this work

Oncology Research 2025, 33(12), 3789-3800. https://doi.org/10.32604/or.2025.067592

Received 07 May 2025; Accepted 19 August 2025; Issue published 27 November 2025

Abstract

Solid tumors comprise the majority of the global cancer burden, with their incidence and associated mortality posing considerable challenges to public health systems. With population growth and aging, the burden of these tumors is anticipated to increase further in the coming decades. The progression of solid tumors depends on dynamic interactions between malignantly transformed cells and the tumor microenvironment (TME). Immune checkpoint inhibitor therapy improves T cell-mediated antitumor activity by suppressing regulatory pathways, such as programmed cell death protein 1/programmed death-ligand 1. Nonetheless, its widespread application is constrained by drug resistance. In this comprehensive review, we elucidate the latest advances in understanding the mechanisms underlying drug resistance, explore pioneering approaches, such as combination therapeutic regimens and nanoscale drug delivery platforms, and propose future avenues for research. These include investigating the intricacies of drug resistance pathways, refining combination therapy strategies, and modulating the TME, along with other key areas.

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Keywords

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