CD4+ and CD8+ T cells have opposing roles in breast cancer progression and outcome

Abstract

// Yi Huang 1,2,* , Chunling Ma 1,3,4,* , Qunyuan Zhang 5 , Jian Ye 1 , Fang Wang 1,6 , Yanping Zhang 7 , Pamela Hunborg 7 , Mark A. Varvares 8 , Daniel F. Hoft 1 , Eddy C. Hsueh 7 and Guangyong Peng 1 1 Department of Internal Medicine, Saint Louis University School of Medicine, Saint Louis, MO, USA 2 Center for Clinical Molecular Medicine, Children’s Hospital of Chongqing Medical University, Chongqing, P. R. China 3 Department of Laboratory Medicine, Women and Children’s Health Care Hospital of Linyi City, Linyi, P. R. China 4 Molecular Biology Experimental Center, Shandong Medical College, Linyi, P. R. China 5 Department of Genetics, Washington University School of Medicine in St. Louis, Saint Louis, MO, USA 6 Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P. R. China 7 Department of Surgery, Saint Louis University School of Medicine, Saint Louis, MO, USA 8 Department of Otolaryngology-Head and Neck Surgery, Saint Louis University School of Medicine, Saint Louis, MO, USA * These authors are contributed equally to this work Correspondence to: Eddy C. Hsueh, email: // Guangyong Peng, email: // Keywords : CD4 + T cells; CD8 + T cells; regulatory T cells; Th17 cells; breast tumor microenvironment Received : February 11, 2015 Accepted : April 09, 2015 Published : April 29, 2015 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.