title: Differences in TCR-Vβ repertoire and effector phenotype between tumor infiltrating lymphocytes and peripheral blood lymphocytes increase with age.
abstract: Tumor infiltrating lymphocytes (TIL) reflect the host's anti-tumor immune response, and can be a valuable predictor of prognosis. However, many properties of TIL are not fully understood. In the present study, TCR-Vβ repertoires of cancer patients were primarily analyzed by flow cytometry. Abnormally expressed TCR-Vβ subfamilies were generally found in both TIL and peripheral blood lymphocytes (PBL) of each patient. Of note, increased patient age was associated with increasingly biased TCR-Vβ repertoire in TIL but not in PBL, and the dispersion degree of the differences of TCR-Vβ subfamilies between TIL and PBL correlated positively with age (P = 0.007). Utilizing immunoscope analysis, we identified the age-related reduction in TCR-Vβ diversity, but polyclonal pattern was predominant in significantly expanded TCR-Vβ subfamilies. In addition, we found that older patients possessed a decreased ratio of CD8+CD62L+ non-effector cells in TIL compared to PBL, implying age-related increase of CD8+CD62L- effector cells in TIL. The colocalization analysis of CD8 and CD3, however, suggested the suppressed activity of these effector cells in tumor microenvironment. These findings further elucidate the properties of TIL, showing an increasing difference between TIL and PBL with age, which may provide insight for the development of effective immunotherapies for cancer patients of different ages.
authors.affiliation: Guangdong Province Key Laboratory for Biotechnology Drug Candidates, Guangzhou, China; School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Shao
authors.affiliation: Guangdong Province Key Laboratory for Biotechnology Drug Candidates, Guangzhou, China; School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, China.
authors.forename: Yusheng
authors.initials: Y
authors.lastname: Ou
authors.affiliation: Guangdong Province Key Laboratory for Biotechnology Drug Candidates, Guangzhou, China; School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Wang
authors.affiliation: Guangdong Province Key Laboratory for Biotechnology Drug Candidates, Guangzhou, China; School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, China.
authors.forename: Han
authors.initials: H
authors.lastname: Shen
authors.affiliation: Guangdong Province Key Laboratory for Biotechnology Drug Candidates, Guangzhou, China; School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, China.
authors.forename: Fenglin
authors.initials: F
authors.lastname: Wu
authors.affiliation: Guangdong Province Key Laboratory for Biotechnology Drug Candidates, Guangzhou, China; School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, China.
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Guangdong Province Key Laboratory for Biotechnology Drug Candidates, Guangzhou, China; School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, China.
authors.forename: Changli
authors.initials: C
authors.lastname: Tao
authors.affiliation: Guangdong Province Key Laboratory for Biotechnology Drug Candidates, Guangzhou, China; School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Guangdong Province Key Laboratory for Biotechnology Drug Candidates, Guangzhou, China; School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, China.
authors.forename: Huaben
authors.initials: H
authors.lastname: Bo
authors.affiliation: Guangdong Province Key Laboratory for Biotechnology Drug Candidates, Guangzhou, China; School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Guangdong Province Key Laboratory for Biotechnology Drug Candidates, Guangzhou, China; School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, China; Southern Medical University, Guangzhou, China.
authors.forename: Shulin
authors.initials: S
authors.lastname: Huang
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D022801:Complementarity Determining Regions / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019041:L-Selectin / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010641:Phenotype; D021381:Protein Transport; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism*
chemical_list: D022801:Complementarity Determining Regions; D016693:Receptors, Antigen, T-Cell, alpha-beta; D019041:L-Selectin