DECIPHERING THE ROLE OF TRANSCRIPTION FACTORS IN HUMAN ANTI-TUMOR CD8 T CELL DYSFUNCTION

Studies in mice, particularly those using chronic LCMV infections, identified expression patterns of transcription factors that characterize dysfunctional or exhausted murine CD8 T cells1,2. However, published data about the role of some of these transcription factors implicated in T cell exhaustion are not clear. We intend to approach this question from a different perspective. First, we analyze transcription factor expression patterns in ex vivo human CD8 T cells obtained from the blood, ascites and solid tumors of ovarian carcinoma patients by flow cytometry. We correlate observed expression patterns to the loss of functional markers, such as cytokine production or granzyme B expression. We then analyze the impact of selected transcription factors on T cell function in vitro by inducing or downregulating their expression in tumor-specific human CD8 T cell clones using lentiviruses. Finally, these modified T cell clones will be compared to their control counterparts for their ability to control tumor growth in a human xenograft model