CXCR5+ CD8+ T cells potently infiltrate pancreatic tumors and present high functionality
Abstract Despite continued improvement in conventional therapy, pancreatic cancer continues to be one of the deadliest tumors worldwide with abysmal 5-year survival rate. New immunotherapeutic strategies that aim at improving antitumor cytotoxic CD8 + T cell responses are being developed in solid tumors. To assist the development of immunotherapies, we investigated the CD8 + T cells in pancreatic cancer patients. Compared to healthy individuals, pancreatic cancer patients presented a significant enrichment in the frequency of CD8 + CXCR5 + T cells. In the tumor microenvironment, the frequencies of CD8 + CXCR5 + T cells were further increased. In most cases, over half of tumor-infiltrating CD8 + T cells were CD8 + CXCR5 + T cells. Compared to the circulating population, the tumor-infiltrating CD8 + CXCR5 + T cells expressed higher levels of PD-1 and TIM-3. Functional analyses demonstrated that upon CD3/CD28 activation, the percentages of TNF-expressing and IFN-γ-expressing cells in CD8 + CXCR5 + T cells were significantly higher than that in CD8 + CXCR5 - T cells. CD8 + CXCR5 + T cells also presented enhanced cytotoxicity than CD8 + CXCR5 - T cells. Upon PD-1 and TIM-3 blockade, the functions of CD8 + CXCR5 + T cells were further improved. The disease-free survival of pancreatic cancer patients following tumor resection was positively correlated with the frequencies of circulating and tumor-infiltrating CD8 + CXCR5 + T cells. Together, our study identified that CD8 + CXCR5 + T cells were a potent subset of CD8 + T cells that were highly enriched in pancreatic cancer patients and could respond to anti-PD-1/anti-TIM-3 blockade by further upregulation in function.
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