鉴定人乳腺癌中表达 CD73 的调节性 Vδ1 γδ T 细胞亚群。
Identification of a regulatory Vδ1 gamma delta T cell subpopulation expressing CD73 in human breast cancer.
机构信息
IRCM, Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Institut Régional du Cancer de Montpellier, Montpellier, France.
Current address: Duve Institute, UCLouvain, Brussels, Belgium.
出版信息
J Leukoc Biol. 2020 Jun;107(6):1057-1067. doi: 10.1002/JLB.3MA0420-278RR. Epub 2020 May 3.
γδ T cells contribute to the immune response against many cancers, notably through their powerful effector functions that lead to the elimination of tumor cells and the recruitment of other immune cells. However, their presence in the tumor microenvironment has been associated with poor prognosis in breast, colon, and pancreatic cancer, suggesting that γδ T cells may also display pro-tumor activities. Here, we identified in blood from healthy donors a subpopulation of Vδ1T cells that represents around 20% of the whole Vδ1 population, expresses CD73, and displays immunosuppressive phenotype and functions (i.e., production of immunosuppressive molecules, such as IL-10, adenosine, and the chemotactic factor IL-8, and inhibition of αβ T cell proliferation). We then found that in human breast tumors, γδ T cells were present particularly in late stage breast cancer samples, and that ∼20% of tumor-infiltrating γδ T cells expressed CD73. Taken together, these results suggest that regulatory γδ T cells are present in the breast cancer microenvironment and may display immunosuppressive functions through the production of immunosuppressive molecules, such as IL-10, IL-8, and adenosine, thus promoting tumor growth.
γδ T 细胞有助于针对多种癌症的免疫反应,特别是通过其强大的效应功能,导致肿瘤细胞的消除和其他免疫细胞的募集。然而,它们在肿瘤微环境中的存在与乳腺癌、结肠癌和胰腺癌的预后不良相关,这表明 γδ T 细胞也可能表现出促肿瘤活性。在这里,我们在健康供体的血液中鉴定出一个 Vδ1T 细胞亚群,该亚群约占整个 Vδ1 群体的 20%,表达 CD73,并表现出免疫抑制表型和功能(即产生免疫抑制分子,如 IL-10、腺苷和趋化因子 IL-8,以及抑制 αβ T 细胞增殖)。然后,我们发现人乳腺癌肿瘤中 γδ T 细胞特别存在于晚期乳腺癌样本中,并且约 20%的肿瘤浸润 γδ T 细胞表达 CD73。综上所述,这些结果表明,调节性 γδ T 细胞存在于乳腺癌微环境中,并可能通过产生免疫抑制分子(如 IL-10、IL-8 和腺苷)来发挥免疫抑制功能,从而促进肿瘤生长。