The effect of TIGIT and PD1 expression on T cell function and prognosis in adult patients with acute myeloid leukemia at diagnosis.

Abstract

T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) is a recently-identified immune checkpoint molecule, and no study ever explores the prognostic significance of TIGIT on bone marrow T cells of newly-diagnosed acute myeloid leukemia (AML) patients. We collected fresh marrow samples from 71 adult AML patients at diagnosis and 31 healthy donors (HDs) to test for TIGIT and PD1 expression in T cells by flow cytometry. Fifteen newly-diagnosed AML patients and six HDs were performed T cell activation in vitro and tested intracellular TNF-α and INF-γ production. Three bone marrow samples of AML patients were performed single cell RNA-sequencing (scRNA-seq). AML patients had significantly higher frequency of TIGIT + cells in CD4 + T cells but similar frequency in CD8 + T cells compared with HDs (p = 0.0006 and 0.77). High percentage of TIGIT + PD1 + in CD8 + T cells independently predicted poor relapse-free survival (RFS) (p = 0.029). Differing from HDs, AML patients had lower level of intracellular TNF-α and INF-γ in TIGIT + cells compared with their TIGIT- counterparts in both CD4 + T and CD8 + T cells. TIGIT + PD1 + CD8 + T cells of patients exhibited significantly lower level of intracellular TNF-α compared with those of HDs (p = 0.024). scRNA-seq data showed that TIGIT + PDCD1 + CD8 + T cells had significantly higher exhaustion score than TIGIT + and PD1 + CD8 + T cells and lower cytotoxic score than TIGIT + CD8 + T cells (p = 0.0016, 0.012 and 0.0014). Therefore, CD8 + T cells with TIGIT and PD1 co-expression exhibited high degree of exhaustion and dysfunctional cytotoxicity, and high percentage of bone marrow TIGIT + PD1 + in CD8 + T cells at diagnosis predicted poor outcome in AML.