CXCR5+ CD8+ T cells potently infiltrate pancreatic tumors and present high functionality

Publication date: 1 December 2017
Source:Experimental Cell Research, Volume 361, Issue 1
Author(s): Minghui Bai, Youwei Zheng, Haichao Liu, Baowei Su, Yong Zhan, Hua He
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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