T cell landscape and dynamics in immunoglobulin light chain amyloidosis before and after daratumumab-based therapy.

Amyloid light-chain (AL) is characterized by the presence of small, poorly proliferating plasma cell clones with the production and deposition of light chains into tissues. T cell changes within the tumour microenvironment in AL are poorly understood. By sequencing at a single-cell level of CD3 ⁺ T cells purified from bone marrow (BM) and blood of newly diagnosed AL patients before and after a combination of daratumumab with cyclophosphamide, bortezomib, and dexamethasone (Dara-BCD), we analysed the transcriptomic features of T cells and found an expansion, activation and type I cytokine upregulation in BM and circulating T cells after the treatment. More prominent changes were shown in CD8 ⁺ T cells. In particular, we found the presence of CD8 ⁺ BM resident memory T cells (T _RM ) with high expression of inhibitory molecules in AL patients at diagnosis. After Dara-BCD, these T _RM cells were quickly activated with downregulation of suppressive molecules and upregulation of IFNG expression. These data collectively demonstrate that Dara-based therapy in patients with AL amyloidosis promotes anti-tumour T cell responses. The similar transcriptomic features of BM and circulating T cells before and after therapy further provide a less invasive approach for molecular monitoring of T cell response in AL amyloidosis.
(© 2021 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)