Local mutational diversity drives intratumoral immune heterogeneity in non-small cell lung cancer
| Autor: | Bo Zhu, Qingzhu Jia, Peter B. Alexander, Wei Wu, Wang Yuqi, Jia Nan Cheng, P. Andrew Futreal, Xuefeng Xia, Chengdu Sun, Zhihua Gong, Yisong Y. Wan, Ji He, Qi-Jing Li, Xin Yi, Huaibo Sun, Yanfang Guan, Ling Yang, Haidong Wang |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Lung Neoplasms Science Biopsy T-Lymphocytes DNA Mutational Analysis General Physics and Astronomy Biology medicine.disease_cause Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Immune system Antigen Antigens Neoplasm Carcinoma Non-Small-Cell Lung Exome Sequencing Tumor Microenvironment medicine Humans Lung cancer Lung Exome sequencing Mutation Multidisciplinary medicine.diagnostic_test Gene Expression Profiling General Chemistry medicine.disease 3. Good health Gene expression profiling 030104 developmental biology Cancer research |
| Zdroj: | Nature Communications Nature Communications, Vol 9, Iss 1, Pp 1-10 (2018) |
| ISSN: | 2041-1723 |
| Popis: | Combining whole exome sequencing, transcriptome profiling, and T cell repertoire analysis, we investigate the spatial features of surgically-removed biopsies from multiple loci in tumor masses of 15 patients with non-small cell lung cancer (NSCLC). This revealed that the immune microenvironment has high spatial heterogeneity such that intratumoral regional variation is as large as inter-personal variation. While the local total mutational burden (TMB) is associated with local T-cell clonal expansion, local anti-tumor cytotoxicity does not directly correlate with neoantigen abundance. Together, these findings caution against that immunological signatures can be predicted solely from TMB or microenvironmental analysis from a single locus biopsy. Intratumoral immunity heterogeneity is poorly characterized. Here the authors apply exome sequencing, transcriptome profiling and T-cell repertoire profiling to multiple loci of non-small-cell lung cancer patients' biopsies and find high spatial immune heterogeneity with local mutational burden correlating with T-cell clonal expansion but not with cytotoxicity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|