Mechanism of lung adenocarcinoma-infiltrating CD8+T cells expressing CD39
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Abstract:
Objective: To study the possible mechanism of lung adenocarcinoma- infiltrating CD8+ T cells expressing CD39. Methods: The transcriptomic data of lung adenocarcinoma (LUAD) tissues and normal lung tissues from the TCGA database were used to analyze the differences in CD39 expression in LUAD tissues and normal lung tissues and its impact on patient prognosis, and to analyze the relationship between CD39 expression and T cell infiltration and activation. Mouse subcutaneous transplantation tumor model was established using LUAD Lewis cells. Flow cytometry was used to detect the expression of CD8+CD39+ T cells in lymph nodes, pancreas and transplantation tumor tissues. Lewis cell culture supernatant was collected as conditioned culture medium (CCM). CD8+T cells and CD11b+ cells were sorted by magnetic activated cell sorting (MACS). Then, CCM and mouse recombinant interleukin-6 (IL-6) were added into the supernatant respectively and contact culture and non-contact culture were carried out to explore the possible mechanism of CD39 expression in CD8+ T cells. Result: The expression of CD39 in LUAD tissues was low (P<0.01). Its expression level was all positively correlated with overall survival (OS) of LUAD patients, the infiltration of T cells and the level of activation (P<0.05 or P<0.01). Flow cytometry results showed that the proportion of CD8+CD39+ T cells in transplantation tumor tissues was significantly higher than that in lymph nodes and spleen (P<0.01). Both CCM and IL-6 could not induce CD8+ T cells to express CD39. Non-contact co-culture of CD11b+ cells and CD8+ T cells could not induce CD8+ T cells to express CD39 either. Direct contact co-culture of CD11b+ cells and CD8+ T cells could induce CD8+ T cells to express CD39(P<0.01). Conclusion: CD11b+ cells induced tumor-infiltrating CD8+ T cells to express CD39 through direct contact, and CD39 may act as a molecule marker of LUAD-specific CD8+ T cells.