CXCR5+CD8+ T cells infiltrate the colorectal tumors and nearby lymph nodes, and are associated with enhanced IgG response in B cells

Colorectal cancer is the third most prevalent cancer type worldwide and contributes to a significant percentage of cancer-related mortality. Recent studies have shown that the CXCR5(+)CD8(+) T cells present more potent proinflammatory function than CXCR5(-)CD8(+) T cells in chronic virus infections and in follicular lymphoma, but the role of CXCR5(+)CD8(+) T cells in colorectal cancer is yet unclear. In this study, we demonstrated that CXCR5(+)CD8(+) T cells were very rare in peripheral blood mononuclear cells from healthy and colorectal cancer individuals, but were significantly enriched in resected tumors and tumor-associated lymph nodes. Compared to CXCR5(-)CD8(+) T cells, the CXCR5(+)CD8(+) T cells demonstrated significantly higher Bcl-6 expression and lower Blimpl expression, suggesting that CXCR5(+)CD8(+) T cells might represent a memory CD8(+) T cell subset. CXCR5(+)CD8(+)T cells also enhanced the IgG expression by autologous B cells. Under ex vivo condition, the CXCR5(+)CD8(+)T cells demonstrated lower degranulation, TNF alpha expression and IFN gamma expression than CXCR5(-)CD8(+) T cells. However, after PMA + ionomycin stimulation, the degranulation and TNF alpha expression by CXCR5(+)CD8(+) T cells were significantly elevated to a level comparable with CXCR5(-)CD8(+) T cells, whereas the IFN gamma expression by PMA + ionomycin-stimulated CXCR5(+)CD8(+) T cells were significantly higher than that by CXCR5(-)CD8(+) T cells. Following long-term TCR-stimulation, CXCR5(-)CD8(+) T cells demonstrated significantly more potent proliferation capacity and higher IFN gamma expression than CXCR5(-)CD8(+) T cells. TCR-stimulated CXCR5(+)CD8(+) T cells also showed a gradual downregulation in CXCR5 expression. We further found that TCR-stimulated CXCR5(+)CD8(+) T cells demonstrated higher granzyme B production and induced more specific lysis of autologous tumor cells than CXCR5(-)CD8(+) T cells. Together, these data demonstrate that CXCR5(+)CD8(+) T cells represent a significant CDS+ T cell subset in colorectal tumors and have the potential to contribute to antitumor immunity, but their specific roles require further studies in vivo.