TIGIT expression is associated with T-cell suppression and exhaustion and predicts clinical outcome and anti-PD-1 response in follicular lymphoma.

Purpose: T cell Ig and ITIM domain (TIGIT), a member of the immune checkpoint family, is important in normal T-cell biology. However, the phenotypical profile and clinical relevance of TIGIT in follicular lymphoma (FL) is largely unknown. Experimental Design: Biopsy specimens from a cohort of 82 FL patients were analyzed using mass cytometry (CyTOF) to explore the phenotype and biological and clinical significance of TIGIT+ T cells. Results: TIGIT is highly expressed on intratumoral T cells and its expression alters T cell phenotype in FL. TIGIT is abundantly expressed on Treg cells, resulting in an enhanced suppressive property. TIGIT expression on non-Treg/TFH T cells defines a population that exhibits an exhausted phenotype. Clinically, increased numbers of TIGIT+ T cells are associated with inferior patient outcomes and poor survival. We observe that anti-PD-1 therapy with pembrolizumab alters the phenotype of TIGIT+ T subsets and identifies a role for CD28 expression on TIGIT+ T cells in treatment response. Conclusion: The present study provides a comprehensive analysis of the phenotypic profile of intratumoral TIGIT+ T subsets and their prognostic relevance in FL. Inhibition of TIGIT signaling may be an additional mechanism to prevent T-cell suppression and exhaustion in B-cell lymphoma.