Comparative analysis of ovarian cancer tumor-infiltrating T cells with those in melanoma and before and after PD-1 blockade
Ilaria Colombo, Ksenia Meteleva, Simone C. Stone, Anjelica Hodgson, Nicolas Jacquelot, Aras Toker, Azin Sayad, Jehan Vakharia, Valentin Sotov, Christine Tran, Hal K. Berman, Stephenie Prokopec, Giselle Boukhaled, Lisa Wang, Pamela Soberanis Pina, Neesha Dhani, Amit M. Oza, Marcus O. Butler, Lillian L. Siu, Ben X. Wang, Pamela S. Ohashi, Stephanie LheureuxAbstract
CD8+ T cells are involved in natural tumor immune surveillance and are known to play a critical role in mediating responses to PD-1 blockade. High grade serous ovarian cancer (HGSOC) exhibits intrinsic resistance to immune-checkpoint inhibitors (ICI), despite the presence of tumor-infiltrating lymphocytes (TIL) in the tumor immune microenvironment (TIME). Here, we characterized the phenotype and frequency of TILs in the tumor samples of patients with HGSOC and compared our findings to TIL from melanoma (MEL), a tumor highly sensitive to ICI. MEL harboured an increased density of CD8+ TILs compared to HGSOC. However, CD8+ T cells from HGSOC tumor samples expressed higher levels of exhaustion markers such as 2B4 and PD-1 compared with the CD8+ MEL TILs, with the evidence for antigen- specific CD8+ TILs. Our study demonstrates that despite the presence of CD8+ T cells that are phenotypically exhausted, there is limited expansion of CD8+ cells after treatment with anti-PD-1 in patients with HGSOC. These data indicate that CD8+ T cells from ovarian cancer express markers associated with antigen specificity, are on the exhaustion trajectory, yet are unable to contribute to a measurable anti-tumor response after PD-1 blockade.