TIGIT Expression Is Associated with T-cell Suppression and Exhaustion and Predicts Clinical Outcome and Anti–PD-1 Response in Follicular Lymphoma

Zhi Zhang Yang, Hyo Jin Kim, Hongyan Wu, Shahrzad Jalali, Xinyi Tang, Jordan E. Krull, Wei Ding, Anne J. Novak, Stephen M. Ansell

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Purpose: T-cell immunoglobulin 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 is largely unknown. Experimental Design: Biopsy specimens from a cohort of 82 patients with follicular lymphoma were analyzed using mass cytometry 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 follicular lymphoma. 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. Conclusions: The current study provides a comprehensive analysis of the phenotypic profile of intratumoral TIGIT+ T subsets and their prognostic relevance in follicular lymphoma. Inhibition of TIGIT signaling may be an additional mechanism to prevent T-cell suppression and exhaustion in B-cell lymphoma.

Original languageEnglish (US)
Pages (from-to)5217-5231
Number of pages15
JournalClinical Cancer Research
Volume26
Issue number19
DOIs
StatePublished - Oct 1 2020

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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