Different expression patterns of VISTA concurrent with PD-1, Tim-3, and TIGIT on T cell subsets in peripheral blood and bone marrow from patients with multiple myeloma

Abstract

V-type immunoglobulin domain-containing suppressor of T cell activation (VISTA) is considered as an immunosuppressive factor and potential therapeutic target for anticancer therapy. However, little is known about VISTA expression and its role in immunosuppression in multiple myeloma (MM). In this study, VISTA expression and co-expression with programmed cell death receptor-1 (PD-1), T cell immunoglobulin mucin-domain-containing-3 (Tim-3), and T cell immunoglobulin and ITIM domain (TIGIT) in CD3+, CD4+, CD8+, and regulatory T (Treg) cells were analyzed in patients with MM by multi-color fluorescent flow cytometry of peripheral blood (PB) and bone marrow (BM) samples from 36 patients with MM and compared to 36 PB samples and 10 BM samples from healthy individuals (HIs), which served as controls. The results demonstrated a significant increased percentage of VISTA co-expression with PD-1, Tim-3, and TIGIT in CD3+, CD4+, CD8+, and Treg cells in PB from MM patients compared with HIs. A similar trend for VISTA+CD8+ T cells was found in BM. Moreover, a trend of a high percentage on VISTA expression and co-expression in PB rather than BM was found. Furthermore, significant positive correlations existed for VISTA expression concurrent with PD-1, Tim-3, and TIGIT in T cell subsets and clinical indicators, including Revised International Staging System (R-ISS) staging of multiple myeloma, Eastern Cooperative Oncology Group (ECOG) score, and beta-2-microglobulin (β2-MG). In conclusion, higher VISTA expression concurrent with PD-1, Tim-3, and TIGIT on T cells, particularly in the PB of patients with MM, may result in T cell exhaustion and dysfunction and be closely associated with disease progression and clinical indicators. Thus, VISTA may be considered a potential target for reversing T cell exhaustion and improving T cell function in MM.

Immune checkpoint expression patterns on T cell subsets in light-chain amyloidosis: VISTA, PD-1, and TIGIT as potential therapeutic targets

“…Both MM and AL belong to malignant plasma cell proliferative diseases, subsequently, we compared the frequencies of T cell subsets expressing VISTA/PD-1/Tim-3/TIGIT in PB between 19 patients with AL amyloidosis and the data from our prior publications from 36 patients with MM. 26 , 29 The findings demonstrated that, in comparison to AL amyloidosis, MM had significantly higher proportions of TIGIT + CD3 + T cell (median: 33.65 vs 25.00, P = .022), TIGIT + CD4 + T cell (median: 23.15 vs 18.70, P = .025), TIGIT + CD8 + T cell (median: 52.15 vs 39.80, P = .003), as well as a higher propensity of TIGIT + Treg. In contrast, AL amyloidosis had a higher tendency of PD-1 + Treg (median: 13.20 vs 10.95, P = 0.016) ( Fig.…”

“…The majority of patients had the λ LC isotype. For comparison with AL amyloidosis, 29 healthy individuals (HIs) and 36 newly diagnosed MM patients 26 with matched age and sex were also included in this study. All patients and HIs gave informed consent in accordance with the Declaration of Helsinki, and the study protocol was approved by the Ethics Committee of the Guangdong Provincial People’s Hospital (approval no.…”

GLT8D2 is a prognostic biomarker and regulator of immune cell infiltration in gastric cancer

“…In the cancer microenvironment, TILs have been demonstrated to play a crucial role in the initiation and progression of cancer ( 37 – 39 ). They may show the characteristics of promoting or inhibiting tumor growth in different types of cancer and different stages of the same type of cancer ( 40 , 41 ). For CD8+ CTLs (cytotoxic T lymphocytes), they act as tumor suppressors by triggering a cytolytic reaction by recognizing tumor-specific antigens presented by the major histocompatibility complex (MHC) ( 42 ).…”

Immune checkpoint inhibitors for multiple myeloma immunotherapy

“…The high expression of VISTA, PD-1, and Tim-3 can be evident on T cells In MM patients, especially in PB, suggesting T cell exhaustion and dysfunction. Therefore targeting VISTA has the potential to reverse T-cell depletion in MM and improve T-cell function [ 85 ]. A 2021 study [ 86 ] analyzed transcriptomic data from a cohort of 718 patients from independent trials and 1654 bone marrow samples from eight clinical trials and concluded that combined VISTA + , CD11b + , and CD8 + cell scores can be used to assess the prognosis of MM and to guide immunotherapy stratification of MM patients.…”