title: CD4+ and CD8+ T cells have opposing roles in breast cancer progression and outcome.
abstract: The Cancer Immunoediting concept has provided critical insights suggesting dual functions of immune system during the cancer initiation and development. However, the dynamics and roles of CD4+ and CD8+ T cells in the pathogenesis of breast cancer remain unclear. Here we utilized two murine breast cancer models (4T1 and E0771) and demonstrated that both CD4+ and CD8+ T cells were increased and involved in immune responses, but with distinct dynamic trends in breast cancer development. In addition to cell number increases, CD4+ T cells changed their dominant subsets from Th1 in the early stages to Treg and Th17 cells in the late stages of the cancer progression. We also analyzed CD4+ and CD8+ T cell infiltration in primary breast cancer tissues from cancer patients. We observed that CD8+ T cells are the key effector cell population mediating effective anti-tumor immunity resulting in better clinical outcomes. In contrast, intra-tumoral CD4+ T cells have negative prognostic effects on breast cancer patient outcomes. These studies indicate that CD4+ and CD8+ T cells have opposing roles in breast cancer progression and outcomes, which provides new insights relevant for the development of effective cancer immunotherapeutic approaches.
authors.affiliation: Department of Internal Medicine, Saint Louis University School of Medicine, Saint Louis, MO, USA.|Center for Clinical Molecular Medicine, Children's Hospital of Chongqing Medical University, Chongqing, P. R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Internal Medicine, Saint Louis University School of Medicine, Saint Louis, MO, USA.|Department of Laboratory Medicine, Women and Children's Health Care Hospital of Linyi City, Linyi, P. R. China.|Molecular Biology Experimental Center, Shandong Medical College, Linyi, P. R. China.
authors.forename: Chunling
authors.initials: C
authors.lastname: Ma
authors.affiliation: Department of Genetics, Washington University School of Medicine in St. Louis, Saint Louis, MO, USA.
authors.forename: Qunyuan
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Internal Medicine, Saint Louis University School of Medicine, Saint Louis, MO, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Ye
authors.affiliation: Department of Internal Medicine, Saint Louis University School of Medicine, Saint Louis, MO, USA.|Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P. R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Surgery, Saint Louis University School of Medicine, Saint Louis, MO, USA.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Surgery, Saint Louis University School of Medicine, Saint Louis, MO, USA.
authors.forename: Pamela
authors.initials: P
authors.lastname: Hunborg
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Saint Louis University School of Medicine, Saint Louis, MO, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Varvares
authors.affiliation: Department of Internal Medicine, Saint Louis University School of Medicine, Saint Louis, MO, USA.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Hoft
authors.affiliation: Department of Surgery, Saint Louis University School of Medicine, Saint Louis, MO, USA.
authors.forename: Eddy C
authors.initials: EC
authors.lastname: Hsueh
authors.affiliation: Department of Internal Medicine, Saint Louis University School of Medicine, Saint Louis, MO, USA.
authors.forename: Guangyong
authors.initials: G
authors.lastname: Peng
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D053208:Kaplan-Meier Estimate; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011379:Prognosis; D016176:T-Lymphocyte Subsets / Q000276:immunology; D059016:Tumor Microenvironment / Q000276:immunology*
keywords: CD4+ T cells; CD8+ T cells; Th17 cells; breast tumor microenvironment; regulatory T cells