The role of transcription factor Runx2 in tumor infiltrating T cells

Adoptive T cell therapy (ACT) is a promising treatment for melanoma patients with a clinical response rate of about 50%. However, half of patients treated do not respond to this therapy, underlining the need for improvement . One of the limitations of ACT is the poor effector function of transferred T cells influenced by the immunosuppressive tumor microenvironment. In order to identify pathways which may contribute to this observation, we used a murine ACT model in which mice bearing established B16 tumors were treated with Pmel T cells which recognize the melanoma antigen gp100 in the context of H-2Db. Pmel T cells were recovered on day 6 and 13, after transfer, from the tumor and spleen of treated mice and their gene expression patterns were compared. We found that 720 genes were differentially expressed by T cells recovered from the tumor site compared to those recovered from the spleen. Amongst the differentially expressed genes were several transcription factors, including Runx2, Rora, E2F1 and Tcf7. After an initial in vivo screen, Runx2 overexpressing Pmels conferred a worse antitumor effect when compared to the control Pmels (median tumor size 30.7 vs 20.7 mm2 respectively on day 7 after T cell transfer, p