Authors
Lu Liu, Dandan Liang, Cui Wang, Jian Li, Jie Tang, Weimin Li, Xijie Yu
Published in
International journal of biological sciences. Volume 22. Issue 13. Pages 6985-7002. Epub Jul 22, 2026.
Abstract
Chimeric antigen receptor (CAR) T cell therapy has achieved remarkable clinical success in hematological malignancies. However, its efficacy in solid tumors such as lung cancer remains constrained by the immunosuppressive tumor microenvironment (TME). Aberrant vascular architecture and dense stroma constitute major physical barriers that hinder CAR T cell infiltration. Additionally, an immunosuppressive cellular network, dominated by myeloid-derived suppressor cells and tumor-associated macrophages, further restricts CAR T cell expansion and function. Moreover, immune checkpoint signaling, inhibitory cytokines, dysregulated chemokine gradients, and metabolic reprogramming under hypoxia collectively create a hostile biochemical and metabolic milieu that drives CAR T cell dysfunction and exhaustion. This review systematically outlines these multifactorial barriers within the lung cancer TME and discusses emerging strategies, including combinatorial approaches, engineered CAR T designs, and microenvironment-modulating platforms, that aim to improve the therapeutic efficacy of CAR T cell therapy in lung cancer.
PMID:
42694665
Bibliographic data and abstract were imported from PubMed on 04 Sep 2026.
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