W105 - Immune Remodelling of the Cancer Immunome After Chemotherapy and Adoptive Cell Transfer

Abstract Text: Precision immunotherapy can potentially improve outcomes of cell therapy as a new frontier in cancer therapeutics. Understanding the effects of various therapies on the human immunome is crucial to enhance efficacy and reduce off-target effects. Adoptive immunotherapy with Epstein-Barr virus (EBV)-specific T cells (EBVST) has known clinical efficacy in EBV-associated nasopharyngeal carcinoma (NPC). As EBV ubiquitously infects humans, this facilitates comparison of both EBV-specific and systemic immune responses in healthy and diseased subjects. We compared global and specific immunity in age matched healthy controls versus NPC patients at baseline, and after standard combination chemotherapy, then sequential infusions of EBVST . Systemic immunity was greatly dysregulated in baseline NPC patients, who displayed reduced naive T cells and B cells compared to healthy controls. Conversely, baseline NPC patients had increased frequencies of T cells expressing the senescence marker CD57, and elevated monocytes and CD16+CD56dim NK cells. Chemotherapy and immunotherapy reduced the frequencies of circulating NK cells and monocytes, while chemotherapy in particular increased the frequency of effector CD8 T cells. EBV-specific responses were detectable in both healthy controls and NPC patients at all treatment timepoints investigated, though there was no significant difference in the frequencies of these subsets between groups. Our results corroborate previous findings of gross immune dysfunction in cancer, particularly involving depletion of naive lymphocytes. Future work will investigate functional differences in EBV-specific responses pre and post-immunotherapy and alterations in interactions between EBV-specific cell subsets and other immune subsets.