title: Tumor-infiltrating γδ T lymphocytes predict clinical outcome in human breast cancer.
abstract: Understanding and dissecting the role of different subsets of regulatory tumor-infiltrating lymphocytes (TILs) in the immunopathogenesis of individual cancer is a challenge for anti-tumor immunotherapy. High levels of γδ regulatory T cells have been discovered in breast TILs. However, the clinical relevance of these intratumoral γδ T cells is unknown. In this study, γδ T cell populations were analyzed by performing immunohistochemical staining in primary breast cancer tissues from patients with different stages of cancer progression. Retrospective multivariate analyses of the correlations between γδ T cell levels and other prognostic factors and clinical outcomes were completed. We found that γδ T cell infiltration and accumulation in breast tumor sites was a general feature in breast cancer patients. Intratumoral γδ T cell numbers were positively correlated with advanced tumor stages, HER2 expression status, and high lymph node metastasis but inversely correlated with relapse-free survival and overall survival of breast cancer patients. Multivariate and univariate analyses of tumor-infiltrating γδ T cells and other prognostic factors further suggested that intratumoral γδ T cells represented the most significant independent prognostic factor for assessing severity of breast cancer compared with the other known factors. Intratumoral γδ T cells were positively correlated with FOXP3(+) cells and CD4(+) T cells but negatively correlated with CD8(+) T cells in breast cancer tissues. These findings suggest that intratumoral γδ T cells may serve as a valuable and independent prognostic biomarker, as well as a potential therapeutic target for human breast cancer.
authors.affiliation: Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, MO 63104, USA.
authors.forename: Chunling
authors.initials: C
authors.lastname: Ma
authors.forename: Qunyuan
authors.initials: Q
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Ye
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Yanping
authors.initials: Y
authors.lastname: Zhang
authors.forename: Eric
authors.initials: E
authors.lastname: Wevers
authors.forename: Theresa
authors.initials: T
authors.lastname: Schwartz
authors.forename: Pamela
authors.initials: P
authors.lastname: Hunborg
authors.forename: Mark A
authors.initials: MA
authors.lastname: Varvares
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Hoft
authors.forename: Eddy C
authors.initials: EC
authors.lastname: Hsueh
authors.forename: Guangyong
authors.initials: G
authors.lastname: Peng
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D001943:Breast Neoplasms / Q000276:immunology* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002465:Cell Movement / Q000276:immunology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy; D008875:Middle Aged; D009367:Neoplasm Staging; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D015996:Survival Rate; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology
chemical_list: D015415:Biomarkers; D016692:Receptors, Antigen, T-Cell, gamma-delta