Unveiling CMV-induced immune alterations in Mycosis Fungoides/Sezary syndrome patients 2508

Abstract Description Increasing evidence suggests that Cytomegalovirus (CMV) latency induces oncomodulation, which could influence the tumor-specific immune response, and potentially the clinical outcome. Our aim was to evaluate the impact of CMV latency on Mycosis Fungoides and Sezary syndrome (MF/SS), the most common cutaneous T-cell lymphomas, also correlated with high CMV infection rates. Using CyTOF, we compared the immune landscape in MF/SS patients (6 PCMV-, 9 PCMV+) to 13 CMV+ healthy donors (HD). We showed that PCMV+ have more Thelper (Th) cells and less monocytes and CD8 T cells compared to both HD and PCMV-. CMV-specific CD8 T cells were higher in PCMV+ compared to HD, but not in Th cells. In PCMV+, PMA+ionomycin-stimulated Th cells produced less cytokines while CD8 T cells were more reactive than in PCMV- and HD. Interestingly, clustering analysis on the Th cells revealed two main subsets, one less differentiated (CCR7highCD45RAhighCD27high), preponderant in PCMV- and another one preeminent in the PCMV+, with a more activated/exhausted phenotype (CD28highCTLA-4highPD-1highCD39high). Single cell Whole Transcriptome and TCR sequencing analyses are ongoing to further characterize the specificities of CMV- and CMV+ patients. Our study showed striking differences of immune responses between MF/SS PCMV+, PCMV- and HD. The peculiar immune landscape in PCMV+ and PCMV- suggests that CMV oncomodulation could have an important role in the MF/SS tumor evolution and the response to treatment. Funding Sources Supported by NIH CA224309, NIH AI153559 Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)