publication . Article . Other literature type . 2016

Landscape of tumor-infiltrating T cell repertoire of human cancers

Jean-Christophe Pignon; Jinzeng Wang; X. Shirley Liu; Bo Li; Qianming Chen; Nir Hacohen; Binbin Wang; Taiwen Li; Taiwen Li; F. Stephen Hodi; ...
Open Access English
  • Published: 30 May 2016 Journal: Nature genetics, volume 48, issue 7, pages 725-732 (issn: 1061-4036, eissn: 1546-1718, Copyright policy)
  • Country: United States
Abstract
We developed a computational method to infer the complementarity-determining region 3 (CDR3) sequences of tumor-infiltrating T cells in 9,142 RNA-seq samples across 29 cancer types. We identified over 600,000 CDR3 sequences, including 15% that were full length. CDR3 sequence length distribution and amino acid conservation, as well as variable gene usage, for infiltrating T cells in many tumors, except in brain and kidney cancers, resembled those for peripheral blood cells from healthy donors. We observed a strong association between T cell diversity and tumor mutation load, and we predicted SPAG5 and TSSK6 as putative immunogenic cancer/testis antigens in multip...
Subjects
Medical Subject Headings: chemical and pharmacologic phenomena
free text keywords: Article, Cancer research, MHC class I, biology.protein, biology, Human leukocyte antigen, Immunology, T cell, medicine.anatomical_structure, medicine, Antigen, Peptide binding, Cancer, medicine.disease, Mutation, medicine.disease_cause, Somatic cell
Related Organizations
38 references, page 1 of 3

Alt, FW. VDJ recombination. Immunol Today. 1992; 13: 306-14 [PubMed]

Davis, MM, Bjorkman, PJ. T-cell antigen receptor genes and T-cell recognition. Nature. 1988; 334: 395-402 [OpenAIRE] [PubMed]

Warren, RL. Exhaustive T-cell repertoire sequencing of human peripheral blood samples reveals signatures of antigen selection and a directly measured repertoire size of at least 1 million clonotypes. Genome Res. 2011; 21: 790-7 [OpenAIRE] [PubMed]

Robins, HS. Comprehensive assessment of T-cell receptor beta-chain diversity in alphabeta T cells. Blood. 2009; 114: 4099-107 [OpenAIRE] [PubMed]

Rosenberg, SA, Restifo, NP, Yang, JC, Morgan, RA, Dudley, ME. Adoptive cell transfer: a clinical path to effective cancer immunotherapy. Nat Rev Cancer. 2008; 8: 299-308 [OpenAIRE] [PubMed]

Sharma, P, Wagner, K, Wolchok, JD, Allison, JP. Novel cancer immunotherapy agents with survival benefit: recent successes and next steps. Nat Rev Cancer. 2011; 11: 805-12 [OpenAIRE] [PubMed]

Pardoll, DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012; 12: 252-64 [OpenAIRE] [PubMed]

Savage, PA. Recognition of a ubiquitous self antigen by prostate cancer-infiltrating CD8+ T lymphocytes. Science. 2008; 319: 215-20 [PubMed]

Obenaus, M. Identification of human T-cell receptors with optimal affinity to cancer antigens using antigen-negative humanized mice. Nat Biotechnol. 2015; 33: 402-7 [PubMed]

Tumeh, PC. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014; 515: 568-71 [OpenAIRE] [PubMed]

Twyman-Saint Victor, C. Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature. 2015; 520: 373-7 [OpenAIRE] [PubMed]

Blachly, JS. Immunoglobulin transcript sequence and somatic hypermutation computation from unselected RNA-seq reads in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A. 2015; 112: 4322-7 [OpenAIRE] [PubMed]

Brown, SD, Raeburn, LA, Holt, RA. Profiling tissue-resident T cell repertoires by RNA sequencing. Genome Med. 2015; 7: 125 [OpenAIRE] [PubMed]

Bolotin, DA. MiTCR: software for T-cell receptor sequencing data analysis. Nat Methods. 2013; 10: 813-4 [OpenAIRE] [PubMed]

Grabherr, MG. Full-length transcriptome assembly from RNA-Seq data without a reference genome. Nat Biotechnol. 2011; 29: 644-52 [OpenAIRE] [PubMed]

38 references, page 1 of 3
Abstract
We developed a computational method to infer the complementarity-determining region 3 (CDR3) sequences of tumor-infiltrating T cells in 9,142 RNA-seq samples across 29 cancer types. We identified over 600,000 CDR3 sequences, including 15% that were full length. CDR3 sequence length distribution and amino acid conservation, as well as variable gene usage, for infiltrating T cells in many tumors, except in brain and kidney cancers, resembled those for peripheral blood cells from healthy donors. We observed a strong association between T cell diversity and tumor mutation load, and we predicted SPAG5 and TSSK6 as putative immunogenic cancer/testis antigens in multip...
Subjects
Medical Subject Headings: chemical and pharmacologic phenomena
free text keywords: Article, Cancer research, MHC class I, biology.protein, biology, Human leukocyte antigen, Immunology, T cell, medicine.anatomical_structure, medicine, Antigen, Peptide binding, Cancer, medicine.disease, Mutation, medicine.disease_cause, Somatic cell
Related Organizations
38 references, page 1 of 3

Alt, FW. VDJ recombination. Immunol Today. 1992; 13: 306-14 [PubMed]

Davis, MM, Bjorkman, PJ. T-cell antigen receptor genes and T-cell recognition. Nature. 1988; 334: 395-402 [OpenAIRE] [PubMed]

Warren, RL. Exhaustive T-cell repertoire sequencing of human peripheral blood samples reveals signatures of antigen selection and a directly measured repertoire size of at least 1 million clonotypes. Genome Res. 2011; 21: 790-7 [OpenAIRE] [PubMed]

Robins, HS. Comprehensive assessment of T-cell receptor beta-chain diversity in alphabeta T cells. Blood. 2009; 114: 4099-107 [OpenAIRE] [PubMed]

Rosenberg, SA, Restifo, NP, Yang, JC, Morgan, RA, Dudley, ME. Adoptive cell transfer: a clinical path to effective cancer immunotherapy. Nat Rev Cancer. 2008; 8: 299-308 [OpenAIRE] [PubMed]

Sharma, P, Wagner, K, Wolchok, JD, Allison, JP. Novel cancer immunotherapy agents with survival benefit: recent successes and next steps. Nat Rev Cancer. 2011; 11: 805-12 [OpenAIRE] [PubMed]

Pardoll, DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012; 12: 252-64 [OpenAIRE] [PubMed]

Savage, PA. Recognition of a ubiquitous self antigen by prostate cancer-infiltrating CD8+ T lymphocytes. Science. 2008; 319: 215-20 [PubMed]

Obenaus, M. Identification of human T-cell receptors with optimal affinity to cancer antigens using antigen-negative humanized mice. Nat Biotechnol. 2015; 33: 402-7 [PubMed]

Tumeh, PC. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014; 515: 568-71 [OpenAIRE] [PubMed]

Twyman-Saint Victor, C. Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature. 2015; 520: 373-7 [OpenAIRE] [PubMed]

Blachly, JS. Immunoglobulin transcript sequence and somatic hypermutation computation from unselected RNA-seq reads in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A. 2015; 112: 4322-7 [OpenAIRE] [PubMed]

Brown, SD, Raeburn, LA, Holt, RA. Profiling tissue-resident T cell repertoires by RNA sequencing. Genome Med. 2015; 7: 125 [OpenAIRE] [PubMed]

Bolotin, DA. MiTCR: software for T-cell receptor sequencing data analysis. Nat Methods. 2013; 10: 813-4 [OpenAIRE] [PubMed]

Grabherr, MG. Full-length transcriptome assembly from RNA-Seq data without a reference genome. Nat Biotechnol. 2011; 29: 644-52 [OpenAIRE] [PubMed]

38 references, page 1 of 3
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