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Overcoming resistance to PD-1 inhibitors: the synergistic anti-tumor effect with inflammatory factors.

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Title: Overcoming resistance to PD-1 inhibitors: the synergistic anti-tumor effect with inflammatory factors.
Authors: Yan H; Wuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China., Wang Y; Institute of Structural Pharmacology & TCM Chemical Biology, Fujian Key Laboratory of Chinese Materia Medica, College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China., Zhu M; Wuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China., Sun D; Wuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: sywysdj@163.com., Li H; Institute of Structural Pharmacology & TCM Chemical Biology, Fujian Key Laboratory of Chinese Materia Medica, College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China. Electronic address: lihua@fjtcm.edu.cn., Chen L; Wuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: syzyclx@163.com.
Source: International immunopharmacology [Int Immunopharmacol] 2025 Dec 03; Vol. 166, pp. 115555. Date of Electronic Publication: 2025 Sep 16.
Publication Type: Journal Article; Review
Language: English
Journal Info: Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 100965259 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-1705 (Electronic) Linking ISSN: 15675769 NLM ISO Abbreviation: Int Immunopharmacol Subsets: MEDLINE
Imprint Name(s): Original Publication: Amsterdam ; New York : Elsevier Science, c2001-
MeSH Terms: Programmed Cell Death 1 Receptor*/antagonists & inhibitors , Programmed Cell Death 1 Receptor*/metabolism , Programmed Cell Death 1 Receptor*/immunology , Neoplasms*/drug therapy , Neoplasms*/immunology , Immune Checkpoint Inhibitors*/therapeutic use , Immune Checkpoint Inhibitors*/pharmacology , Drug Resistance, Neoplasm*/drug effects , Inflammation Mediators*, Humans ; Animals ; B7-H1 Antigen/antagonists & inhibitors ; B7-H1 Antigen/metabolism ; B7-H1 Antigen/immunology ; Drug Synergism ; Cytokines/metabolism
Abstract: Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Tumors can evade immunity through the PD-1/PD-L1 pathway. PD-1/PD-L1 inhibitors have demonstrated therapeutic efficacy across a broad range of cancer types. However, the poor response of PD-1/PD-L1 inhibitors monotherapy limits their clinical application. PD-1/PD-L1 inhibitors and inflammatory factors exhibit synergistic anti-tumor effects. Inflammatory factors can regulate the expression of PD-L1 and affect the occurrence and development of tumors. Therefore, the combination of inflammatory factors and PD-1 inhibitors is a reasonable way to overcome the primary resistance of PD-1/PD-L1 inhibitors. However, the potential clinical risk of cytokine storm associated with this combination strategy warrants significant attention. This article reviews the interaction between inflammatory factors and the PD-1/PD-L1 pathway and discusses the possibility of combining inflammatory factors and PD-1 inhibitors to reverse this resistance.
(Copyright © 2025 Elsevier B.V. All rights reserved.)
Contributed Indexing: Keywords: Anti-tumor; Inflammatory factors; PD-1 inhibitors; Primary resistance
Substance Nomenclature: 0 (Programmed Cell Death 1 Receptor)
0 (Immune Checkpoint Inhibitors)
0 (B7-H1 Antigen)
0 (PDCD1 protein, human)
0 (CD274 protein, human)
0 (Inflammation Mediators)
0 (Cytokines)
Entry Date(s): Date Created: 20250917 Date Completed: 20251104 Latest Revision: 20251104
Update Code: 20251104
DOI: 10.1016/j.intimp.2025.115555
PMID: 40961752
Database: MEDLINE
Description
Abstract:Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br />Tumors can evade immunity through the PD-1/PD-L1 pathway. PD-1/PD-L1 inhibitors have demonstrated therapeutic efficacy across a broad range of cancer types. However, the poor response of PD-1/PD-L1 inhibitors monotherapy limits their clinical application. PD-1/PD-L1 inhibitors and inflammatory factors exhibit synergistic anti-tumor effects. Inflammatory factors can regulate the expression of PD-L1 and affect the occurrence and development of tumors. Therefore, the combination of inflammatory factors and PD-1 inhibitors is a reasonable way to overcome the primary resistance of PD-1/PD-L1 inhibitors. However, the potential clinical risk of cytokine storm associated with this combination strategy warrants significant attention. This article reviews the interaction between inflammatory factors and the PD-1/PD-L1 pathway and discusses the possibility of combining inflammatory factors and PD-1 inhibitors to reverse this resistance.<br /> (Copyright © 2025 Elsevier B.V. All rights reserved.)
ISSN:1878-1705
DOI:10.1016/j.intimp.2025.115555