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

被引:4
作者
Wang, Jinghua [1 ]
Zhao, Yujie [2 ]
Liao, Pengjun [1 ]
Huang, Shuxin [2 ]
Huang, Youxue [2 ]
Chen, Shaohua [2 ]
Li, Yangqiu [2 ]
Zhong, Liye [1 ]
机构
[1] Southern Med Univ, Guangdong Prov Peoples Hosp, Guangdong Acad Med Sci, Dept Hematol, Guangzhou, Peoples R China
[2] Jinan Univ, Inst Hematol, Sch Med, Key Lab Regenerat Med,Minist Educ, Guangzhou, Peoples R China
来源
BLOOD SCIENCE | 2024年 / 6卷 / 01期
基金
中国国家自然科学基金;
关键词
AL amyloidosis; PD-1; TIGIT; Tim-3; VISTA; NIVOLUMAB; TOLERANCE; ANTIGEN; SURVEILLANCE; ROLES;
D O I
10.1097/BS9.0000000000000181
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Amyloid light chain (AL) amyloidosis is a rare plasma cell dyscrasia with dismal prognosis. This study aims to investigate the T-cell immune checkpoint expression patterns in systemic AL amyloidosis and its relationship with clinicobiological traits. We examined the frequencies of V-domain immunoglobulin suppressor of T cell activation+ (VISTA+), programmed cell death 1+ (PD-1+), T cell immunoglobulin and mucin-domain-containing-3+ (Tim-3+), T cell immunoreceptor with Ig and ITIM domains+ (TIGIT+) T cells in peripheral blood (PB) and bone marrow (BM) from 19 patients with newly diagnosed AL amyloidosis. Patients with AL amyloidosis had significantly higher percentages of VISTA+ and PD-1+ T cells in PB than healthy individuals (HIs), with no statistical differences in BM. The percentages of some double-positive T cells in PB were also considerably higher in AL amyloidosis than those in HIs. Additionally, the patients with renal involvement had more PD-1+ and TIGIT+ T cells than the patients without, and PD-1+CD3+%, PD-1+CD4+%, PD-1+Treg% were positively correlated with 24-hour proteinuria levels. Furthermore, the AL amyloidosis patients had higher counts of PD-1+ Treg in PB than multiple myeloma (MM) patients, while the MM patients had higher counts of TIGIT+ T cells than AL amyloidosis patients. Collectively, this is the first report of elevated proportions of VISTA+ and PD-1+ T cells in PB of AL amyloidosis patients, indicating an immunosuppressive milieu, and the increased PD-1+ and TIGIT+ T cells were associated with renal damage. VISTA, PD-1, and TIGIT may be potential targets for reversing T-cell exhaustion in AL amyloidosis.
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页数:10
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共 56 条
[1]   Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes [J].
Agata, Y ;
Kawasaki, A ;
Nishimura, H ;
Ishida, Y ;
Tsubata, T ;
Yagita, H ;
Honjo, T .
INTERNATIONAL IMMUNOLOGY, 1996, 8 (05) :765-772
[2]   Tumor antigen-specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired [J].
Ahmadzadeh, Mojgan ;
Johnson, Laura A. ;
Heemskerk, Bianca ;
Wunderlich, John R. ;
Dudley, Mark E. ;
White, Donald E. ;
Rosenberg, Steven A. .
BLOOD, 2009, 114 (08) :1537-1544
[3]   Checkpoint Inhibitors in Multiple Myeloma: Intriguing Potential and Unfulfilled Promises [J].
Alkharabsheh, Omar ;
Trisel, Zachary ;
Badami, Sunil ;
Aljama, Mohammed A. ;
Sidiqi, M. Hasib .
CANCERS, 2022, 14 (01)
[4]   Marrow-Infiltrating Regulatory T Cells Correlate with the Presence of Dysfunctional CD4+PD-1+ Cells and Inferior Survival in Patients with Newly Diagnosed Multiple Myeloma [J].
Alrasheed, Nouf ;
Lee, Lydia ;
Ghorani, Ehsan ;
Henry, Jake Y. ;
Conde, Lucia ;
Chin, Melody ;
Galas-Filipowicz, Daria ;
Furness, Andrew J. S. ;
Chavda, Selina J. ;
Richards, Huw ;
De-Silva, Dunnya ;
Cohen, Oliver C. ;
Patel, Dominic ;
Brooks, Anthony ;
Rodriguez-Justo, Manuel ;
Pule, Martin ;
Herrero, Javier ;
Quezada, Sergio A. ;
Yong, Kwee L. .
CLINICAL CANCER RESEARCH, 2020, 26 (13) :3443-3454
[5]   Lag-3, Tim-3, and TIGIT: Co-inhibitory Receptors with Specialized Functions in Immune Regulation [J].
Anderson, Ana C. ;
Joller, Nicole ;
Kuchroo, Vijay K. .
IMMUNITY, 2016, 44 (05) :989-1004
[6]   Nivolumab for Relapsed/Refractory Classic Hodgkin Lymphoma After Failure of Autologous Hematopoietic Cell Transplantation: Extended Follow-Up of the Multicohort Single-Arm Phase II CheckMate 205 Trial [J].
Armand, Philippe ;
Engert, Andreas ;
Younes, Anas ;
Fanale, Michelle ;
Santoro, Armando ;
Zinzani, Pier Luigi ;
Timmerman, John M. ;
Collins, Graham P. ;
Ramchandren, Radhakrishnan ;
Cohen, Jonathon B. ;
De Boer, Jan Paul ;
Kuruvilla, John ;
Savage, Kerry J. ;
Trneny, Marek ;
Shipp, Margaret A. ;
Kato, Kazunobu ;
Sumbul, Anne ;
Farsaci, Benedetto ;
Ansell, Stephen M. .
JOURNAL OF CLINICAL ONCOLOGY, 2018, 36 (14) :1428-+
[7]   CTLA-4 and PD-1 Pathways Similarities, Differences, and Implications of Their Inhibition [J].
Buchbinder, Elizabeth I. ;
Desai, Anupam .
AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS, 2016, 39 (01) :98-106
[8]   Immunotherapy of Cancer by Targeting Regulatory T cells [J].
Chen, Bo-Jin ;
Zhao, Jing-Wen ;
Zhang, Da-Hong ;
Zheng, Ai-Hong ;
Wu, Guo-Qing .
INTERNATIONAL IMMUNOPHARMACOLOGY, 2022, 104
[9]   Checkpoint Inhibition in Myeloma: Opportunities and Challenges [J].
Costa, Federica ;
Das, Rituparna ;
Bailur, Jithendra Kini ;
Dhodapkar, Kavita ;
Dhodapkar, Madhav V. .
FRONTIERS IN IMMUNOLOGY, 2018, 9
[10]   The cellular immune system in myelomagenesis: NK cells and T cells in the development of MM and their uses in immunotherapies [J].
Dosani, T. ;
Carlsten, M. ;
Maric, I. ;
Landgren, O. .
BLOOD CANCER JOURNAL, 2015, 5 :e306-e306