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

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 st...

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Main Authors: Shuxin Huang, Yujie Zhao, Pengjun Liao, Jinghua Wang, Zhiyan Li, Jiaxiong Tan, Xianfeng Zha, Shaohua Chen, Yangqiu Li, Liye Zhong
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-11-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2022.1014904/full
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author Shuxin Huang
Yujie Zhao
Pengjun Liao
Jinghua Wang
Zhiyan Li
Jiaxiong Tan
Xianfeng Zha
Shaohua Chen
Yangqiu Li
Liye Zhong
author_facet Shuxin Huang
Yujie Zhao
Pengjun Liao
Jinghua Wang
Zhiyan Li
Jiaxiong Tan
Xianfeng Zha
Shaohua Chen
Yangqiu Li
Liye Zhong
author_sort Shuxin Huang
collection DOAJ
description 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.
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spelling doaj.art-5110badacf4846429b369b7a516e343e2022-12-22T04:35:21ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-11-011210.3389/fonc.2022.10149041014904Different 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 myelomaShuxin Huang0Yujie Zhao1Pengjun Liao2Jinghua Wang3Zhiyan Li4Jiaxiong Tan5Xianfeng Zha6Shaohua Chen7Yangqiu Li8Liye Zhong9Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, ChinaKey Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, ChinaDepartment of Hematology, Guangdong Academy of Medical Sciences, Guangdong Provincial People’s Hospital, Guangzhou, ChinaDepartment of Hematology, Guangdong Academy of Medical Sciences, Guangdong Provincial People’s Hospital, Guangzhou, ChinaKey Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, ChinaDepartment of Hematology, First Affiliated Hospital, Jinan University, Guangzhou, ChinaDepartment of Clinical Laboratory, First Affiliated Hospital, Jinan University, Guangzhou, ChinaKey Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, ChinaKey Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, ChinaDepartment of Hematology, Guangdong Academy of Medical Sciences, Guangdong Provincial People’s Hospital, Guangzhou, ChinaV-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.https://www.frontiersin.org/articles/10.3389/fonc.2022.1014904/fullMMT cell exhaustionVISTAPD-1TIM-3TIGIT
spellingShingle Shuxin Huang
Yujie Zhao
Pengjun Liao
Jinghua Wang
Zhiyan Li
Jiaxiong Tan
Xianfeng Zha
Shaohua Chen
Yangqiu Li
Liye Zhong
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
Frontiers in Oncology
MM
T cell exhaustion
VISTA
PD-1
TIM-3
TIGIT
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic MM
T cell exhaustion
VISTA
PD-1
TIM-3
TIGIT
url https://www.frontiersin.org/articles/10.3389/fonc.2022.1014904/full
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