Strategies to Overcome Immunotherapy Resistance in Non-Small Cell Lung Cancer: Targeting Non-Cancer Cells
10.3971/j.issn.1000-8578.2025.25.0506
- VernacularTitle:克服非小细胞肺癌中的免疫治疗耐药的策略——针对非癌细胞
- Author:
Runzhi CHEN
1
;
Chang XUE
1
;
Xiaoyu LI
1
;
Yuanxiang LI
1
;
Sheng HU
1
Author Information
1. Department of Medical Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430079, China.
- Publication Type:SPECIALFEATURE
- Keywords:
Non-small cell lung cancer;
Immune checkpoint inhibitor;
Cell therapy;
Vaccine;
Biological therapy
- From:
Cancer Research on Prevention and Treatment
2025;52(11):926-936
- CountryChina
- Language:Chinese
-
Abstract:
One of the key mechanisms underlying resistance against immunotherapy is the reduction in the abundance and functional capacity of immune cells within the tumor microenvironment (TME). Accordingly, the development of novel antibodies and small-molecule agents that target multiple co-inhibitory molecules—whether employed as monotherapies or in combination—holds promise for reinvigorating exhausted T cells and restoring antitumor immune responses. In addition, exploring agonists targeting co-stimulatory molecules represents a promising strategy to enhance the secondary signals necessary for T cell activation and thereby facilitates tumor eradication. However, careful attention must be given to potential toxicities associated with these agents. Furthermore, this review highlights the emerging therapeutic potential of cancer vaccines, oncolytic viruses, diverse cellular therapies, and other innovative strategies designed to augment the efficacy of immunotherapy in non-small cell lung cancer (NSCLC). Moreover, we discuss therapeutic strategies targeting non-proliferating TME components, including cancer-associated fibroblasts (CAFs) and the extracellular matrix (ECM), and hypoxia-alleviating agents and immune homeostasis-supporting probiotics, all aimed at enhancing anti-tumor immunity. In summary, this article emphasizes the critical importance of integrating therapeutics with complementary mechanisms of action while maintaining the balance between efficacy and tolerability in the advancement of precise and effective immunotherapy in NSCLC to an unprecedented level.
