title: Tumor-infiltrating lymphocytes in colorectal tumors display a diversity of T cell receptor sequences that differ from the T cells in adjacent mucosal tissue.
abstract: Tumors from colorectal cancer (CRC) are generally immunogenic and commonly infiltrated with T lymphocytes. However, the details of the adaptive immune reaction to these tumors are poorly understood. We have accrued both colon tumor samples and adjacent healthy mucosal samples from 15 CRC patients to study lymphocytes infiltrating these tissues. We apply a method for detailed sequencing of T-cell receptor (TCR) sequences from tumor-infiltrating lymphocytes (TILs) in CRC tumors at high throughput to probe T-cell clones in comparison with the TCRs from adjacent healthy mucosal tissue. In parallel, we captured TIL counts using standard immunohistochemistry. The variation in diversity of the TIL repertoire was far wider than the variation of T-cell clones in the healthy mucosa, and the oligoclonality was higher on average in the tumors. However, the diversity of the T-cell repertoire in both CRC tumors and healthy mucosa was on average 100-fold lower than in peripheral blood. Using the TCR sequences to identify and track clones between mucosal and tumor samples, we determined that the immune response in the tumor is different than in the adjacent mucosal tissue, and the number of shared clones is not dependent on distance between the samples. Together, these data imply that CRC tumors induce a specific adaptive immune response, but that this response differs widely in strength and breadth between patients.
authors.affiliation: Adaptive Biotechnologies, 1551 Eastlake Ave, Seattle, WA 98102, USA.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Sherwood
authors.forename: Ryan O
authors.initials: RO
authors.lastname: Emerson
authors.forename: Dominique
authors.initials: D
authors.lastname: Scherer
authors.forename: Nina
authors.initials: N
authors.lastname: Habermann
authors.forename: Katharina
authors.initials: K
authors.lastname: Buck
authors.forename: Jürgen
authors.initials: J
authors.lastname: Staffa
authors.forename: Cindy
authors.initials: C
authors.lastname: Desmarais
authors.forename: Niels
authors.initials: N
authors.lastname: Halama
authors.forename: Dirk
authors.initials: D
authors.lastname: Jaeger
authors.forename: Peter
authors.initials: P
authors.lastname: Schirmacher
authors.forename: Esther
authors.initials: E
authors.lastname: Herpel
authors.forename: Matthias
authors.initials: M
authors.lastname: Kloor
authors.forename: Alexis
authors.initials: A
authors.lastname: Ulrich
authors.forename: Martin
authors.initials: M
authors.lastname: Schneider
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: Ulrich
authors.forename: Harlan
authors.initials: H
authors.lastname: Robins
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005260:Female; D057166:High-Throughput Screening Assays; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000473:pathology; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
chemical_list: D011948:Receptors, Antigen, T-Cell