REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1633100
Mechanisms and clinical advancements of cell-based immunotherapies in nonsmall cell lung cancer: an integrated perspective
Provisionally accepted
Lixian Yang1
Yaoyao Gong2*- 1Shandong University, Jinan, China
- 2The Second Hospital of Shandong University, Jinan, China
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Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide, with only modest improvements in survival despite advances in conventional therapies. Cell-based immunotherapy, which utilizes ex vivo expanded or genetically modified immune cells, has emerged as a promising therapeutic alternative. Approaches such as natural killer (NK) cells, tumor-infiltrating lymphocytes (TILs), dendritic cell (DC)-based vaccines, cytokine-induced killer (CIK) cells, and chimeric antigen receptor T (CAR-T) cells have shown encouraging potential in preclinical and early clinical studies. However, their clinical efficacy in NSCLC is significantly constrained by multiple factors, including the immunosuppressive tumor microenvironment (TME), intratumoral antigenic heterogeneity, and limited persistence and expansion of adoptively transferred cells. To address these barriers, advances in cellular engineering, rational combinatorial regimens, and refined patient selection strategies are actively being explored. This review provides a critical overview of the current landscape of cell-based therapies in NSCLC, focusing on recent breakthroughs, persistent limitations, and evolving strategies to enhance therapeutic outcomes. By contextualizing these developments, we aim to clarify the translational potential of cellular immunotherapy and its role in redefining the treatment paradigm for NSCLC.
Keywords: Non-small cell lung cancer, clinical trials, cell therapy, lymphocyteactivated killer cell therapy, tumor-infiltrating lymphocyte cell therapy, dendritic cellcytokine-induced killer cell therapy, chimeric antigen receptor T cell therapy Author (Year) Study Design Patient Population Treatment Regimen Key Outcomes Challenges and Indication
Received: 22 May 2025; Accepted: 31 Jul 2025.
Copyright: © 2025 Yang and Gong. 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: Yaoyao Gong, The Second Hospital of Shandong University, Jinan, China
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