Transcriptome profiling of tumor-infiltrating lymphocyte-mediated cytotoxicity against patient-derived lung cancer organoids

Non-small cell lung cancer (NSCLC) is a leading cause of cancer mortality, and therapies utilizing tumor-infiltrating lymphocytes (TILs) show significant promise. However, molecular signatures defining a productive TIL-mediated response remain poorly characterized. Here, we establish a patient-derived organoid and autologous TIL co-culture platform to show that expanded TILs mediate potent, specific cytotoxicity against NSCLC organoids. This functional response is associated with a crucial shift in T-cell states from proliferative towards effector memory phenotypes and involves activating key signaling networks, including the TNF and IL-17 pathways. Furthermore, T-cell receptor (TCR) analysis confirms the expansion process selectively enriches tumor-associated clonotypes, resulting in a more focused repertoire. This work delineates the transcriptional and clonal signatures of an effective anti-tumor immune response, providing a robust framework to guide next-generation personalized TIL therapies.

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Publication Details

Journal
Communications Biology
Published
2025-11-23
DOI
https://doi.org/10.1038/s42003-025-09188-0
Citations
1
Primary Topic
Cancer Immunotherapy and Biomarkers
Type
article
Field-Weighted Citation Impact
1.05

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article

Transcriptome profiling of tumor-infiltrating lymphocyte-mediated cytotoxicity against patient-derived lung cancer organoids

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1 citations
Communications Biology
Cancer Immunotherapy and Biomarkers
1.05
article

Transcriptome profiling of tumor-infiltrating lymphocyte-mediated cytotoxicity against patient-derived lung cancer organoids

Qumiao Xu, Qinghua Hou, Zhiyuan Qin, Hongchang Zhang, Xian Lin, Haozhen Liu, Qiao Li, Zhuojue Guan, Xiaoqiang Li, Chao Chen, Junhui Chen, Jixian Liu, Jianyi Yang, Haocheng Du, Yanling Li
article en
1 citations

Abstract

Non-small cell lung cancer (NSCLC) is a leading cause of cancer mortality, and therapies utilizing tumor-infiltrating lymphocytes (TILs) show significant promise. However, molecular signatures defining a productive TIL-mediated response remain poorly characterized. Here, we establish a patient-derived organoid and autologous TIL co-culture platform to show that expanded TILs mediate potent, specific cytotoxicity against NSCLC organoids. This functional response is associated with a crucial shift in T-cell states from proliferative towards effector memory phenotypes and involves activating key signaling networks, including the TNF and IL-17 pathways. Furthermore, T-cell receptor (TCR) analysis confirms the expansion process selectively enriches tumor-associated clonotypes, resulting in a more focused repertoire. This work delineates the transcriptional and clonal signatures of an effective anti-tumor immune response, providing a robust framework to guide next-generation personalized TIL therapies.

Communications BiologyVol. 8(1)
Shenzhen University (CN), University of Michigan (US), Michigan Medicine (US), Peking University Shenzhen Hospital (CN), University of Chinese Academy of Sciences (CN)
Sanming Project of Medicine in Shenzhen
Openalex Percentile: Top 16%
Cancer Immunotherapy and Biomarkers
1.05
DOIOpen Access PDFOpenAlex
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