title: Interleukin 2 and interleukin 10 function synergistically to promote CD8+T cell cytotoxicity, which is suppressed by regulatory T cells in breast cancer.
abstract: The precise role of interleukin (IL)-10 in breast cancer is not clear. Previous studies suggested a tumor-promoting role of IL-10 in breast cancer, whereas recent discoveries that IL-10 activated and expanded tumor-resident CD8+T cells challenged the traditional view. Here, we investigated the role of IL-10 in HLA-A2-positive breast cancer patients with Grade III, Stage IIA or IIB in-situ and invasive ductal carcinoma, and compared it with that of IL-2, the canonical CD8+T cell growth factor. We first observed that breast cancer patients presented higher serum levels of IL-2 and IL-10 than healthy controls. Upon prolonged TCR stimulation, peripheral blood CD8+T cells from breast cancer patients tended to undergo apoptosis, which could be prevented by the addition of IL-2 and/or IL-10. The cytotoxicity of TCR-activated CD8+T cells was also enhanced by exogenous IL-2 and/or IL-10. Interestingly, IL-2 and IL-10 demonstrated synergistic effects, since the enhancement in CD8+T cell function when both cytokines were added was greater than the sum of the improvements mediated by each individual cytokine. IL-10 by itself could not promote the proliferation of CD8+T cells but could significantly enhance IL-2-mediated promotion of CD8+T cell proliferation. In addition, the cytotoxicity of tumor-infiltrating CD8+T cells in breast tumor was elevated when both IL-2 and IL-10 were present but not when either one was absent. This synergistic effect was stopped by CD4+CD25+regulatory T cells (Treg), which depleted IL-2 in a cell number-dependent manner. Together, these results demonstrated that IL-2 and IL-10 could work synergistically to improve the survival, proliferation, and cytotoxicity of activated CD8+T cells, an effect suppressible by CD4+CD25+Treg cells.
authors.affiliation: Department of General Surgery, The Second People's Hospital of Yunnan Province, Kunming, Yunnan 650021, China.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Li
authors.affiliation: Science and Education Division, The Second People's Hospital of Yunnan Province, 176 Qingnian Road, Kunming, Yunnan 650021, China. Electronic address: pinglukm003@qq.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Lu
authors.affiliation: Department of General Surgery, The Second People's Hospital of Yunnan Province, Kunming, Yunnan 650021, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of General Surgery, The Second People's Hospital of Yunnan Province, Kunming, Yunnan 650021, China.
authors.forename: Wanfu
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, The Second People's Hospital of Yunnan Province, Kunming, Yunnan 650021, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Yang
authors.affiliation: Department of General Surgery, The Second People's Hospital of Yunnan Province, Kunming, Yunnan 650021, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chu
authors.affiliation: Department of General Surgery, The Second People's Hospital of Yunnan Province, Kunming, Yunnan 650021, China.
authors.forename: Kaiyuan
authors.initials: K
authors.lastname: Luo
mesh_terms: D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology*; D015704:CD4 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004357:Drug Synergism; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
chemical_list: D015704:CD4 Antigens; C508609:IL10 protein, human; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D016753:Interleukin-10
keywords: Breast cancer; CD8+ T cell; Interleukin 10; Interleukin 2