Abstract Text: Within the last few years there has been increased awareness of immune-mediated adverse events associated with cancer immunotherapies. Basic research into how the immune system is responding to these treatments and promoting new autoimmune-like diseases has been limited. We explored immune-mediated adverse events during immunotherapy in autoimmune-prone mice by assessing autoantibody production, kidney function, and immune cell phenotypes. Changes in activation and exhaustion via flow cytometry were also assessed within CXCR5+ and CXCR5- T cell subsets. Our previous research showed that CXCR5+CD8+ T cells drive autoimmune disease by promoting antibody class-switching and plasma cell differentiation. We observed elevated inhibitory marker expression in autoimmune CXCR5+CD4 and CXCR5+CD8 T cells that could be reactivated during therapy, potentially driving immune-mediated adverse events. CXCR5+CD8+ T cells also upregulate markers of exhaustion during chronic infection and cancer; the reactivation of these cells is a good cancer prognosis during immunotherapy. We tested whether autoimmune CXCR5+CD8+ T cells induce immune-mediated adverse events following checkpoint blockade treatments, and whether these events mimic autoimmune pathology. These studies suggest a deeper understanding of the relationship between immune-mediated adverse events and specific immune cell populations. This research may increase our future ability to better modulate immune-mediated adverse events within patients being treated for cancer.
