Activated Tim-3/Galectin-9 participated in the development of multiple myeloma by negatively regulating CD4 T cells

被引:8
作者
Zhang, Rui [1 ,2 ]
Chen, Shuang [1 ,2 ]
Luo, Tingting [1 ,2 ]
Guo, Sha [1 ,2 ]
Qu, Jianhua [1 ,2 ]
机构
[1] Xinjiang Med Univ, Affiliated Hosp 1, Ctr Hematol, Urumqi, Xinjing, Peoples R China
[2] Hematol Inst Xinjiang Uygur Autonomous Reg, Urumqi, Xinjiang, Peoples R China
基金
中国国家自然科学基金;
关键词
PREDICTS POOR-PROGNOSIS; TIM-3; EXPRESSION;
D O I
10.1080/16078454.2023.2288481
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The interaction between Tim-3 on T cells and its ligand Galectin-9 negatively regulates the cellular immune response. However, the regulation of Tim-3/Galectin-9 on CD4 T cell subsets in multiple myeloma (MM) remains unclear. The aim of this study was to investigate the relationship between the regulation of CD4 T cell subsets by the Tim-3/Galectin-9 pathway and clinical prognostic indicators in MM. Tim-3/Galectin-9 were detected by flow cytometry, PCR and ELISA in 60 MM patients and 40 healthy controls, and its correlation with clinical prognostic parameters was analyzed. The expressions of Tim-3 on CD4 T cells, Galectin-9 mRNA in PBMC and level of Galectin-9 protein in serum were significantly elevated in MM patients, especially those with poor prognostic indicators. In MM patients, Tim-3 was highly expressed on the surfaces of Th1, Th2, and Th17 cells, but lowly expressed on Treg. Moreover, level of cytokine IFN-gamma in serum was negatively correlated with Tim-3+Th1 cell and Galectin-9mRNA, Galectin-9 protein level. In addition, cell culture experiments showed that the anti-tumor effect and the ability to secrete IFN-gamma were restored by blocking the Tim-3/Galectin-9 pathway. In MM patients, Tim-3/Galectin-9 is elevated and associated with disease progression, by inhibiting the cytotoxic function of Th1, and also promoting Th2 and Th17 to be involved in immune escape of MM. Therefore, Tim-3/Galectin-9 may serve as a new immunotherapeutic target for MM patients.
引用
收藏
页数:16
相关论文
共 45 条
  • [1] Tim-3 finds its place in the cancer immunotherapy landscape
    Acharya, Nandini
    Sabatos-Peyton, Catherine
    Anderson, Ana Carrizosa
    [J]. JOURNAL FOR IMMUNOTHERAPY OF CANCER, 2020, 8 (01)
  • [2] Osteoclasts promote immune suppressive microenvironment in multiple myeloma: therapeutic implication
    An, Gang
    Acharya, Chirag
    Feng, Xiaoyan
    Wen, Kenneth
    Zhong, Mike
    Zhang, Li
    Munshi, Nikhil C.
    Qiu, Lugui
    Tai, Yu-Tzu
    Anderson, Kenneth C.
    [J]. BLOOD, 2016, 128 (12) : 1590 - 1603
  • [3] Functional expression of Tim-3 on blasts and clinical impact of its ligand galectin-9 in myelodysplastic syndromes
    Asayama, Toshio
    Tamura, Hideto
    Ishibashi, Mariko
    Kuribayashi-Hamada, Yasuko
    Onodera-Kondo, Asaka
    Okuyama, Namiko
    Yamada, Akiko
    Shimizu, Masumi
    Moriya, Keiichi
    Takahashi, Hidemi
    Inokuchi, Koiti
    [J]. ONCOTARGET, 2017, 8 (51) : 88904 - 88917
  • [4] Quantitative and functional characteristics of circulating and bone marrow PD-1-and TIM-3-positive T cells in treated multiple myeloma patients
    Batorov, Egor, V
    Aristova, Tatiana A.
    Sergeevicheva, Vera V.
    Sizikova, Svetlana A.
    Ushakova, Galina Y.
    Pronkina, Natalia, V
    Shishkova, Irina, V
    Shevela, Ekaterina Y.
    Ostanin, Alexander A.
    Chernykh, Elena R.
    [J]. SCIENTIFIC REPORTS, 2020, 10 (01)
  • [5] IL-10-producing T cells and their dual functions
    Bedke, Tanja
    Muscate, Franziska
    Soukou, Shiwa
    Gagliani, Nicola
    Huber, Samuel
    [J]. SEMINARS IN IMMUNOLOGY, 2019, 44
  • [6] Butcher Matthew J, 2021, Fac Rev, V10, P30, DOI 10.12703/r/10-30
  • [7] Microbiota-driven interleukin-17-producing cells and eosinophils synergize to accelerate multiple myeloma progression
    Calcinotto, Arianna
    Brevi, Arianna
    Chesi, Marta
    Ferrarese, Roberto
    Perez, Laura Garcia
    Grioni, Matteo
    Kumar, Shaji
    Garbitt, Victoria M.
    Sharik, Meaghen E.
    Henderson, Kimberly J.
    Tonon, Giovanni
    Tomura, Michio
    Miwa, Yoshihiro
    Esplugues, Enric
    Flavell, Richard A.
    Huber, Samuel
    Canducci, Filippo
    Rajkumar, Vincent S.
    Bergsagel, P. Leif
    Bellone, Matteo
    [J]. NATURE COMMUNICATIONS, 2018, 9
  • [8] T helper 17 (Th17) cells and interleukin-17 (IL-17) in cancer
    Chang, Seon Hee
    [J]. ARCHIVES OF PHARMACAL RESEARCH, 2019, 42 (07) : 549 - 559
  • [9] Th17 cell frequency and IL-17A production in peripheral blood of patients with non-small-cell lung cancer
    Chen, Gang
    Zhang, Pei-Gang
    Li, Jun-Sheng
    Duan, Jing-Jing
    Su, Wen
    Guo, Shi-Ping
    Wang, Yan-Feng
    Sun, Jun-Ning
    Yang, Xiao-Tang
    [J]. JOURNAL OF INTERNATIONAL MEDICAL RESEARCH, 2020, 48 (06)
  • [10] Management of relapsed and refractory multiple myeloma: novel agents, antibodies, immunotherapies and beyond
    Chim, C. S.
    Kumar, S. K.
    Orlowski, R. Z.
    Cook, G.
    Richardson, P. G.
    Gertz, M. A.
    Giralt, S.
    Mateos, M. V.
    Leleu, X.
    Anderson, K. C.
    [J]. LEUKEMIA, 2018, 32 (02) : 252 - 262