REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicCancer Immunity, Modern Radiotherapy and Immunotherapy: A Journey into Cancer Treatment InnovationView all 7 articles
Overcoming Resistance to Immune Checkpoint Inhibitor in Non-Small Cell Lung Cancer: The Promise of Combination Therapy
Provisionally accepted
- Tongling People's Hospital, Tongling, China
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The clinical application of immune checkpoint inhibitor (ICI) has profoundly reshaped the therapeutic landscape of non-small cell lung cancer (NSCLC), heralding a new era of immunotherapy in oncology. However, despite the durable and remarkable clinical benefits observed in a subset of patients, a considerable proportion exhibit primary or acquired resistance, substantially limiting overall therapeutic efficacy. Immune resistance has emerged as one of the central challenges in ICI-based NSCLC treatment, stemming from an incomplete understanding of ICI mechanisms of action and the highly heterogeneous and dynamically complex nature of the NSCLC tumor microenvironment (TME). This review provides a comprehensive overview of the diverse molecular and cellular mechanisms underlying ICI resistance in NSCLC, highlights recent advances in combination therapeutic strategies aimed at overcoming resistance, and discusses the opportunities and challenges associated with their clinical translation and application.
Keywords: NSCLC, ICI, Immune Resistance, Tumor Microenvironment, combination therapy
Received: 25 Aug 2025; Accepted: 23 Oct 2025.
Copyright: © 2025 Shi, Deng, Pan, Chen, Wang and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xuebing Shi, sxbtlph@163.com
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