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Global analysis of shared T cell specificities in human non-small cell lung cancer enables HLA inference and antigen discovery.
Chiou, Shin-Heng; Tseng, Diane; Reuben, Alexandre; Mallajosyula, Vamsee; Molina, Irene S; Conley, Stephanie; Wilhelmy, Julie; McSween, Alana M; Yang, Xinbo; Nishimiya, Daisuke; Sinha, Rahul; Nabet, Barzin Y; Wang, Chunlin; Shrager, Joseph B; Berry, Mark F; Backhus, Leah; Lui, Natalie S; Wakelee, Heather A; Neal, Joel W; Padda, Sukhmani K; Berry, Gerald J; Delaidelli, Alberto; Sorensen, Poul H; Sotillo, Elena; Tran, Patrick; Benson, Jalen A; Richards, Rebecca; Labanieh, Louai; Klysz, Dorota D; Louis, David M; Feldman, Steven A; Diehn, Maximilian; Weissman, Irving L; Zhang, Jianjun; Wistuba, Ignacio I; Futreal, P Andrew; Heymach, John V; Garcia, K Christopher; Mackall, Crystal L; Davis, Mark M.
Affiliation
  • Chiou SH; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA 94305, USA.
  • Tseng D; Department of Medicine, Division of Oncology, Stanford University, Stanford, CA 94305, USA.
  • Reuben A; Department of Thoracic Head and Neck Medical Oncology, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Mallajosyula V; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA 94305, USA.
  • Molina IS; Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901, USA.
  • Conley S; Institute for Stem Cell Biology and Regenerative Medicine Institute, Stanford University, Stanford, CA 94305, USA.
  • Wilhelmy J; Stanford Genome Technology Center, Stanford University, Stanford, CA 94305, USA.
  • McSween AM; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA 94305, USA.
  • Yang X; Department of Molecular and Cellular Physiology and Structural Biology, Stanford University, Stanford, CA 94305, USA.
  • Nishimiya D; Department of Molecular and Cellular Physiology and Structural Biology, Stanford University, Stanford, CA 94305, USA.
  • Sinha R; Institute for Stem Cell Biology and Regenerative Medicine Institute, Stanford University, Stanford, CA 94305, USA.
  • Nabet BY; Department of Radiation Oncology, Stanford University, Stanford, CA 94305, USA.
  • Wang C; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA 94305, USA.
  • Shrager JB; Department of Cardiothoracic Surgery - Thoracic Surgery, Stanford University, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford, CA 94305, USA.
  • Berry MF; Department of Cardiothoracic Surgery - Thoracic Surgery, Stanford University, Stanford, CA 94305, USA.
  • Backhus L; Department of Cardiothoracic Surgery - Thoracic Surgery, Stanford University, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford, CA 94305, USA.
  • Lui NS; Department of Cardiothoracic Surgery - Thoracic Surgery, Stanford University, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford, CA 94305, USA.
  • Wakelee HA; Department of Medicine, Division of Oncology, Stanford University, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford, CA 94305, USA.
  • Neal JW; Department of Medicine, Division of Oncology, Stanford University, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford, CA 94305, USA.
  • Padda SK; Department of Medicine, Division of Oncology, Stanford University, Stanford, CA 94305, USA.
  • Berry GJ; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
  • Delaidelli A; Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, BC V5Z 1L3, Canada.
  • Sorensen PH; Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, BC V5Z 1L3, Canada.
  • Sotillo E; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA 94305, USA.
  • Tran P; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA 94305, USA.
  • Benson JA; Department of Cardiothoracic Surgery - Thoracic Surgery, Stanford University, Stanford, CA 94305, USA.
  • Richards R; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA 94305, USA; Department of Pediatrics, Stanford University, Stanford, CA 94305, USA.
  • Labanieh L; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA 94305, USA; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
  • Klysz DD; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA 94305, USA.
  • Louis DM; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA 94305, USA.
  • Feldman SA; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA 94305, USA.
  • Diehn M; Institute for Stem Cell Biology and Regenerative Medicine Institute, Stanford University, Stanford, CA 94305, USA; Department of Radiation Oncology, Stanford University, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford, CA 94305, USA.
  • Weissman IL; Institute for Stem Cell Biology and Regenerative Medicine Institute, Stanford University, Stanford, CA 94305, USA.
  • Zhang J; Department of Thoracic Head and Neck Medical Oncology, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Genomic Medicine, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Wistuba II; Department of Translational Molecular Pathology, Division of Pathology and Laboratory Medicine, MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Futreal PA; Department of Genomic Medicine, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Heymach JV; Department of Thoracic Head and Neck Medical Oncology, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Garcia KC; Department of Molecular and Cellular Physiology and Structural Biology, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Mackall CL; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA 94305, USA; Department of Pediatrics, Stanford University, Stanford, CA 94305, USA; Department of Medicine, Stanford University, Stanford, CA 94305, USA.
  • Davis MM; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA. Electronic a
Immunity ; 54(3): 586-602.e8, 2021 03 09.
Article de En | MEDLINE | ID: mdl-33691136
ABSTRACT
To identify disease-relevant T cell receptors (TCRs) with shared antigen specificity, we analyzed 778,938 TCRß chain sequences from 178 non-small cell lung cancer patients using the GLIPH2 (grouping of lymphocyte interactions with paratope hotspots 2) algorithm. We identified over 66,000 shared specificity groups, of which 435 were clonally expanded and enriched in tumors compared to adjacent lung. The antigenic epitopes of one such tumor-enriched specificity group were identified using a yeast peptide-HLA A∗0201 display library. These included a peptide from the epithelial protein TMEM161A, which is overexpressed in tumors and cross-reactive epitopes from Epstein-Barr virus and E. coli. Our findings suggest that this cross-reactivity may underlie the presence of virus-specific T cells in tumor infiltrates and that pathogen cross-reactivity may be a feature of multiple cancers. The approach and analytical pipelines generated in this work, as well as the specificity groups defined here, present a resource for understanding the T cell response in cancer.
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Mots clés

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Lymphocytes T / Récepteur lymphocytaire T antigène, alpha-bêta / Carcinome pulmonaire non à petites cellules / Cartographie épitopique / Déterminants antigéniques des lymphocytes T / Tumeurs du poumon Type d'étude: Prognostic_studies Limites: Humans Langue: En Journal: Immunity Sujet du journal: ALERGIA E IMUNOLOGIA Année: 2021 Type de document: Article Pays d'affiliation: États-Unis d'Amérique

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Lymphocytes T / Récepteur lymphocytaire T antigène, alpha-bêta / Carcinome pulmonaire non à petites cellules / Cartographie épitopique / Déterminants antigéniques des lymphocytes T / Tumeurs du poumon Type d'étude: Prognostic_studies Limites: Humans Langue: En Journal: Immunity Sujet du journal: ALERGIA E IMUNOLOGIA Année: 2021 Type de document: Article Pays d'affiliation: États-Unis d'Amérique