double positive cd4cd8 αβ t cells a new tumor-reactive population in human melanomas双正cd4cd8αβt细胞新的tumor-reactive人口人类黑色素瘤.pdfVIP

Double Positive CD4CD8 ab T Cells: A New Tumor- Reactive Population in Human Melanomas 1 ` 1,2 1 1 1,3 Juliette Desfranc¸ois , Agnes Moreau-Aubry , Virginie Vignard , Yann Godet , Amir Khammari , ´ 1,3,4, Francine Jotereau1,2, Nadine Gervois1,2* Brigitte Dreno ´ ´ 1 UMR INSERM, U892, Nantes, France, 2 Universite de Nantes, Faculte des Sciences, Nantes, France, 3 Unit of Skin Cancer, Centre Hospitalier Universitaire de Nantes, Nantes, France, 4 GMP Unit of Cellular Therapy, Centre Hospitalier Universitaire de Nantes, Nantes, France Abstract Background: Double positive (DP) CD4CD8 Tab cells have been reported in normal individuals as well as in different pathological conditions including inflammatory diseases, viral infections and cancer, but their function remains to be elucidated. We recently reported the increased frequency of DP Tab cells in human breast pleural effusions. This manuscript addresses the question of the existence and above all the role of this non-conventional DP sub-population among tumor associated lymphocytes in melanomas. Methodology/Principal Findings: We analyzed the intratumoral cell infiltrate in solid metastasis (n = 6) and tumor invaded lymph nodes (n = 26) samples from melanomas patients by multiparametric cytometry. Here we documented for the first time significant increased frequency of DP T cells in about 60% of melanoma tumors compared to blood samples. Interestingly, a high proportion of these cells produced TNF-a in response to autologous melanoma cell lines. Besides, they are