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

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

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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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] 学术成果认领
作者单位 Department of Hematology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China [1] Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, China [2]
栏目名称 Research Article
DOI 10.1097/BS9.0000000000000181
发布时间 2025-02-25
基金项目
This work was supported by the National Natural Science Foundation of China the Science and Technology Program of Guangzhou the High-level Hospital Construction Project of Guangdong Provincial People's Hospital the Medical Scientific Research Foundation of Guangdong Province
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