CD4+ and CD8+ T cells have opposing roles in breast cancer progression and outcome
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Yi Huang1,2,*, Chunling Ma1,3,4,*, Qunyuan Zhang5, Jian Ye1, Fang Wang1,6, Yanping Zhang7, Pamela Hunborg7, Mark A. Varvares8, Daniel F. Hoft1, Eddy C. Hsueh7 and Guangyong Peng1
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
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
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.
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