Comprehensive T cell repertoire characterization of non-small cell lung cancer
| Autor: | Roy S. Herbst, James P. Allison, Kelly Quek, Edwin R. Parra, Samantha Tippen, Harlan Robins, Chi Wan Chow, Alexandre Reuben, Runzhe Chen, Erik Yusko, Padmanee Sharma, Xizeng Mao, Jiexin Zhang, John V. Heymach, Patrick Hwu, Boris Sepesi, Jun Li, Yuanqing Ye, Jianhua Zhang, Humam Kadara, Carmen Behrens, Rebecca Thornton, Farrah Kheradmand, Neda Kalhor, Xin Hu, Latasha Little, P. Andrew Futreal, Paul Scheet, Alexandra Snyder, Tina Cascone, Sharon Benzeno, Don L. Gibbons, Won-Chul Lee, Xiaoke Liu, Veera Baladandayuthapani, Xifeng Wu, Jack Lee, Cesar A. Moran, Ignacio I. Wistuba, Ara A. Vaporciyan, Ali Jalali, Chunlin Wang, Junya Fujimoto, Xingzhi Song, Heather Lin, Curtis Gumbs, Mark M. Davis, Feng Wang, Ryan O. Emerson, Chantale Bernatchez, Jennifer A. Wargo, Shin Heng Chiou, Chang-Jiun Wu, Stephen G. Swisher, Marissa Vignali, Rachel M. Gittelman, Agda Karina Eterovic, Jianjun Zhang |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Lung Neoplasms medicine.medical_treatment T-Lymphocytes General Physics and Astronomy Lymphocyte Activation 0302 clinical medicine Carcinoma Non-Small-Cell Lung Cancer genomics T-cell receptor lcsh:Science Lung Multidisciplinary Middle Aged 3. Good health ErbB Receptors medicine.anatomical_structure 030220 oncology & carcinogenesis Tumour immunology Female Adult T cell Science General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Immune system Antigen medicine Carcinoma Humans Lymphocyte Count Lung cancer Aged business.industry General Chemistry Immunotherapy medicine.disease Survival Analysis respiratory tract diseases Clone Cells 030104 developmental biology Mutation Cancer research lcsh:Q business Non-small-cell lung cancer |
| Zdroj: | Nature Communications Nature Communications, Vol 11, Iss 1, Pp 1-13 (2020) |
| ISSN: | 2041-1723 |
| Popis: | Immunotherapy targeting T cells is increasingly utilized to treat solid tumors including non-small cell lung cancer (NSCLC). This requires a better understanding of the T cells in the lungs of patients with NSCLC. Here, we report T cell repertoire analysis in a cohort of 236 early-stage NSCLC patients. T cell repertoire attributes are associated with clinicopathologic features, mutational and immune landscape. A considerable proportion of the most prevalent T cells in tumors are also prevalent in the uninvolved tumor-adjacent lungs and appear specific to shared background mutations or viral infections. Patients with higher T cell repertoire homology between the tumor and uninvolved tumor-adjacent lung, suggesting a less tumor-focused T cell response, exhibit inferior survival. These findings indicate that a concise understanding of antigens and T cells in NSCLC is needed to improve therapeutic efficacy and reduce toxicity with immunotherapy, particularly adoptive T cell therapy. Relevant features of T cell repertoire in human cancer remain to be delineated. Here the authors show, by TCR sequencing in a large cohort of lung cancer patients, that while a majority of T cell clones are shared between tumor and adjacent lung tissue, less frequent tumor-unique T cell clones correlate with worse prognosis. |
| Databáze: | OpenAIRE |
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