Open AccessT cell landscape and dynamics in immunoglobulin light chain amyloidosis before and after daratumumab‐based therapy
Author(s) -
Wang Yujia,
Xu Lushuang,
Zhao Weijia,
Chen Xiaojie,
Wen Lei,
Duan Wenbing,
Yu XiaoJuan,
De Zhou Fu,
Liu Yang,
Hao Jie,
Huang Xiaojun,
Lu Jin,
Ge Qing
Publication year - 2021
Publication title -
clinical and translational medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.125
H-Index - 1
ISSN - 2001-1326
DOI - 10.1002/ctm2.582
Subject(s) - daratumumab , downregulation and upregulation , cd8 , cancer research , bortezomib , t cell , immunoglobulin light chain , amyloidosis , multiple myeloma , al amyloidosis , immunology , medicine , antibody , biology , immune system , pathology , biochemistry , gene
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.