CD8+CXCR5+ T cells in tumor-draining lymph nodes are highly activated and predict better prognosis in colorectal cancer

Abstract

Tumor-draining lymph nodes (TDLNs) are the primary sites of tumor antigen presentation, as well as the origin of metastasis in most cases. Hence, the type and function of immune cells in TDLNs are critical to the microenvironment and potentially affect the clinical outcome of the malignancy. CD8⁺CXCR5⁺ T cells are recently described to present high effector functions in infectious diseases, but their role in colorectal cancer (CRC) remains unclear. In forty-four Stage III CRC patients, we examined the CD8⁺CXCR5⁺ T cells in blood, tumor, and TDLN. CD8⁺CXCR5⁺ T cells represented lass than 2% of CD3⁺ T cells in blood, but a much larger population in tumor. In TDLN, the CD8⁺CXCR5⁺ T cells represented the vast majority of CD8⁺ T cells and between 9.3% and 32.9% of CD3⁺ T cells. The prevalence of CD8⁺CXCR5⁺ T cells in tumor was not associated with their frequency in peripheral blood, but was positively correlated with their frequency in TDLN. The transcription of effector genes, including IFNG, TNF, IL2, PRF1, and GZMB, and exhaustion markers, including PD1, TIM3, 2B4, and LAG3, were examined in CD8⁺CXCR5⁺ T cells and CD8⁺CXCR5^- T cells. With a few exceptions, CD8⁺CXCR5⁺ T cell presented significantly higher effector gene expression, and significantly lower exhaustion marker expression than their CXCR5^- counterparts. In addition, the prognosis of CRC patients was positively associated with the frequency of TDLN CD8⁺CXCR5⁺ T cells, and with the expression of IFNG, PRF1, and GZMB expression by tumor and TDLN CD8⁺CXCR5⁺ T cells. Together, these results demonstrated that CD8⁺CXCR5⁺ T cells were significant participants of CRC-associated immunity and could potentially serve as therapeutic options.

Keywords: CD8(+)CXCR5(+) T cells; Colorectal cancer; Tumor-draining lymph nodes.