Follicular cytotoxic CD8 T cells present high cytokine expression, and are more susceptible to Breg-mediated suppression in non-small cell lung cancer.

Tumor-infiltrating CD8 T cells are instrumental to antitumor immunity. In this study, we found that a subset of CXCR5-expressing CD8 T cells, termed follicular cytotoxic T (Tfc) cells, potently infiltrated the untreated tumors from non-small cell lung cancer (NSCLC) patients. On average, Tfc cells represented 14% of total tumor-infiltrating CD8 T cells and 6.6% of total tumor-infiltrating lymphocytes. Upon antigenic stimulation, Tfc cells presented significantly higher degranulation and stronger release of proinflammatory cytokines, including IFNg, IL2, and TNF, and the pleiotropic cytokine IL10 than non-Tfc cells. However, the expression of granzyme B and perforin was significantly lower in Tfc cells than in non-Tfc CD8 T cells. B regulatory (Breg) cells could significantly suppress proinflammatory cytokine production in both Tfc cells and non-Tfc CD8 T cells, but in Tfc cells, a lower concentration was required. Moreover, Breg cells could significantly elevate IL10 expression by Tfc cells but could not affect IL-10 expression by non-Tfc CD8 T cells. The neutralization of IL10 significantly reduced the extent of Breg-mediated regulation. Together, this study demonstrated that Tfc cells represented a significant proportion of tumor-infiltrating CD8 T cells in lung carcinoma. These Tfc cells were different from non-Tfc CD8 T cells in terms of cytokine expression and granzyme and perforin release and were more susceptible to Breg-mediated suppression in an IL-10-dependent manner.