T cell senescence and T cell exhaustion as potential biomarkers of progression-free and overall survival in patients with recurrent ovarian cancer treated with anti-PD1 combination therapy

This study aimed to determine if immune senescence and T-cell exhaustion are biomarkers for response to immunotherapy in ovarian cancer patients. Our group recently published a phase II clinical trial (NCT02853318) demonstrating the efficacy of the combination of pembrolizumab, bevacizumab, and oral metronomic cyclophosphamide in recurrent ovarian cancer patients. The ORR was 47.5%, and the median PFS was 10 months. We categorized patients as responders (R) and non-responders (NR) based on survival, and R had a PFS of 20.2 months and OS of 29.1 months, compared to a PFS of 5.27 months and OS of 12.5 months in NR patients. Cytotoxic chemotherapy used in the frontline and recurrent setting can induce immune cell aging and, by that, decrease response to subsequent immunotherapy. In this study, we sought to determine if immune cell aging, measured by senescent and exhausted T cells, played a role in response to this combination regimen.