title: T cell receptor β-chain repertoire analysis reveals intratumour heterogeneity of tumour-infiltrating lymphocytes in oesophageal squamous cell carcinoma.
abstract: Oesophageal squamous cell carcinoma (ESCC) has a generally poor prognosis, due to the lack of effective treatment methods. Immunotherapeutic approaches based on tumour-infiltrating lymphocytes (TILs) have demonstrated that durable responses are produced in some patients with solid tumours, which suggests the potential feasibility of clinical application of immunotherapy for ESCC. However, many of the basic characteristics of TILs in ESCC are poorly understood, including clonality, specificity and spatial heterogeneity of the response of TILs, which depends on the interaction between antigens and T cell receptors (TCRs). We used ultra-deep sequencing of rearranged genes in TCR β-chain (TCRβ) to profile the basic characteristics of T cells in tumour tissues (four to six regions from each tumour) as well as matched adjacent normal tissue and peripheral blood from seven patients diagnosed with primary ESCC. We found that T cell clones within ESCCs were quite different from those of the peripheral blood and even the adjacent normal tissues in general. Although there was a relatively higher degree of overlap of intratumoural TCRβ repertoires than those between the tumour and other tissues, intratumoural TCRβ repertoires were spatially heterogeneous. Due to the restricted sampling, high-throughput TCRβ sequencing could characterize the diversity and composition of a limited (compartment-dependent) fraction of the respective T cell clones in any individual ESCC, expanding our understanding of immune behaviour and immune response and shedding more light on ESCC immunotherapy. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital and Institute, Beijing, People's Republic of China.|Department of Gastroenterology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, People's Republic of China.
authors.forename: Zengchao
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital and Institute, Beijing, People's Republic of China.
authors.forename: Chaoting
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital and Institute, Beijing, People's Republic of China.
authors.forename: Yaqi
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Anyang Cancer Hospital, Anyang, Henan, People's Republic of China.
authors.forename: Ruiping
authors.initials: R
authors.lastname: Xu
authors.affiliation: Department of Gastroenterology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, People's Republic of China.
authors.forename: Changqing
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Gastroenterology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, People's Republic of China.
authors.forename: Ziping
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital and Institute, Beijing, People's Republic of China.
authors.forename: Zheming
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital and Institute, Beijing, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Ke
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology*; D004938:Esophageal Neoplasms / Q000235:genetics / Q000473:pathology*; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta
keywords: T cell receptors; high-throughput sequencing; intratumour heterogeneity; oesophageal squamous cell carcinoma; tumour-infiltrating lymphocytes