In the dynamic field of hematology and oncology, innovative treatments for systemic amyloid light chain (AL) amyloidosis are essential. Recent research, led by Professor Yangqiu Li from the Institute of Hematology, School of Medicine, Jinan University,, explores immune checkpoint expression patterns in AL amyloidosis. This study investigates VISTA+, PD-1+, Tim-3+, and TIGIT+ T cells in newly diagnosed patients, highlighting the immunosuppressive environment of the disease.The findings reveal the potential of targeting VISTA, PD-1, and TIGIT to reverse T-cell exhaustion, offering new therapeutic avenues.

This study aims to investigate T-cell immune checkpoint expression patterns in systemic light-chain (AL) amyloidosis and their association with clinicobiological traits. Specifically, the focus is on V-domain immunoglobulin suppressor of T cell activation (VISTA), programmed cell death 1 (PD-1), and T cell immunoreceptor with Ig and ITIM domains (TIGIT) as potential therapeutic targets.

The study included 19 newly diagnosed AL amyloidosis patients, 29 healthy individuals (HIs), and 36 newly diagnosed multiple myeloma (MM) patients. Peripheral blood (PB) and bone marrow (BM) samples were collected and analyzed using flow cytometry to determine the frequencies of VISTA+, PD-1+, Tim-3+, and TIGIT+ T cells.

The research results have shed light on the immunological landscape in AL amyloidosis, demonstrating that VISTA+ and PD-1+ T cells were significantly increased in the peripheral blood of patients with this condition. This increase suggests the presence of an immunosuppressive environment. Furthermore, the study found a correlation between PD-1+ and TIGIT+ T cells and the extent of renal damage in AL amyloidosis patients, indicating a potential role of these immune markers in disease progression. Interestingly, the immune checkpoint patterns observed in AL amyloidosis were distinct from those in multiple myeloma (MM). Specifically, AL amyloidosis was characterized by higher counts of PD-1+ regulatory T cells (Treg), while MM was associated with higher counts of TIGIT+ T cells. These findings underscore the unique immunological features of AL amyloidosis and could have implications for targeted therapeutic approaches.

(Blood Science. 6(1):e00181, January 2024.)

The study identifies VISTA, PD-1, and TIGIT as key immune checkpoints involved in the immunosuppressive environment of AL amyloidosis. These checkpoints could be promising therapeutic targets to reverse T-cell exhaustion and improve treatment outcomes in AL amyloidosis.

This study highlights the distinct immune checkpoint expression patterns in AL amyloidosis and their clinical implications. Targeting VISTA, PD-1, and TIGIT could offer new therapeutic strategies to enhance T-cell activity and combat the immunosuppressive environment in AL amyloidosis. Further research with larger patient cohorts and longer follow-up is necessary to validate these findings and explore the potential of combined checkpoint inhibition therapies.