MiR-7 缺陷促进 CD4(+)T 细胞的 Th1 极化，并增强肺癌过继细胞疗法的抗肿瘤效果

Adoptive-cell-therapy (ACT) is important therapeutic approach against cancer.

We previously showed that miR-7 deficiency endowed CD4 + T cells with hyperactivation status in liver injury.

However, whether CD4 + T cells with miR-7 deficiency could elicit antitumor effect in ACT is still unclear. Naïve CD4 + CD62L hi T cells were purified from CD45. 2 WT or CD45. 2 miR-7 def mice and transferred into syngeneic CD45. 1WT mice bearing with lung tumor cells. The infiltration and function of T cells were measured by FCM and immunofluorescence assay.

And naïve CD4 + CD62L hi T cells were purified from CD45. 2 WT or CD45. 2 miR-7 def mice, then the cells were activated with CD3 antibody plus CD28 antibody in vitro for 24 h. Then, the cultured supernatant of LLC tumor cells or cytokines IFN-γ and IL-12 was added to establish Th1 polarization. Under these conditions, Th1 polarization-related molecules in these cells were analyzed by flow cytometry.

Our data demonstrated a significant reduction in the growth and metastasis of lung cancer cells in the miR-7 def CD4 + T cell-transferred group, accompanied by a significant enhancement in the infiltration, proliferation, activation, and Th1 polarization of CD4 + T cells.

Moreover, we observed the proliferation; activation of tumor-infiltrating CD8 + T cells was significantly increased in the local tumor of the CD45. 2 miR-7 def CD4 + T cell-transferred group, compared to the CD45. 2 WT CD4 + T cell-transferred group.

It is noteworthy that MAPK4, a target molecule of miR-7, was upregulated in CD4 + T cells from lung tumor tissues, resulting in an altered transduction of phosphorylation of NF-κB as well as AKT and ERK in vivo and in vitro. miR-7 deficiency promoted Th1-polarization of CD4 + T cells and elicited effective antitumor immune responses in ACT.