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

Abstract 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...

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Autores principales:	Yujia Wang, Lushuang Xu, Weijia Zhao, Xiaojie Chen, Lei Wen, Wenbing Duan, Xiao‐Juan Yu, Fu‐ De Zhou, Yang Liu, Jie Hao, Xiaojun Huang, Jin Lu, Qing Ge
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	bone marrow resident memory T cells daratumumab immunoglobulin light chain amyloidosis single‐cell RNA sequencing T cells Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/b2b678204e184ca281d2bd9be93f879a
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spelling	oai:doaj.org-article:b2b678204e184ca281d2bd9be93f879a2021-11-30T07:25:38ZT cell landscape and dynamics in immunoglobulin light chain amyloidosis before and after daratumumab‐based therapy2001-132610.1002/ctm2.582https://doaj.org/article/b2b678204e184ca281d2bd9be93f879a2021-11-01T00:00:00Zhttps://doi.org/10.1002/ctm2.582https://doaj.org/toc/2001-1326Abstract 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 (TRM) with high expression of inhibitory molecules in AL patients at diagnosis. After Dara‐BCD, these TRM 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.Yujia WangLushuang XuWeijia ZhaoXiaojie ChenLei WenWenbing DuanXiao‐Juan YuFu‐ De ZhouYang LiuJie HaoXiaojun HuangJin LuQing GeWileyarticlebone marrow resident memory T cellsdaratumumabimmunoglobulin light chain amyloidosissingle‐cell RNA sequencingT cellsMedicine (General)R5-920ENClinical and Translational Medicine, Vol 11, Iss 11, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	bone marrow resident memory T cells daratumumab immunoglobulin light chain amyloidosis single‐cell RNA sequencing T cells Medicine (General) R5-920
spellingShingle	bone marrow resident memory T cells daratumumab immunoglobulin light chain amyloidosis single‐cell RNA sequencing T cells Medicine (General) R5-920 Yujia Wang Lushuang Xu Weijia Zhao Xiaojie Chen Lei Wen Wenbing Duan Xiao‐Juan Yu Fu‐ De Zhou Yang Liu Jie Hao Xiaojun Huang Jin Lu Qing Ge T cell landscape and dynamics in immunoglobulin light chain amyloidosis before and after daratumumab‐based therapy
description	Abstract 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 (TRM) with high expression of inhibitory molecules in AL patients at diagnosis. After Dara‐BCD, these TRM 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.
format	article
author	Yujia Wang Lushuang Xu Weijia Zhao Xiaojie Chen Lei Wen Wenbing Duan Xiao‐Juan Yu Fu‐ De Zhou Yang Liu Jie Hao Xiaojun Huang Jin Lu Qing Ge
author_facet	Yujia Wang Lushuang Xu Weijia Zhao Xiaojie Chen Lei Wen Wenbing Duan Xiao‐Juan Yu Fu‐ De Zhou Yang Liu Jie Hao Xiaojun Huang Jin Lu Qing Ge
author_sort	Yujia Wang
title	T cell landscape and dynamics in immunoglobulin light chain amyloidosis before and after daratumumab‐based therapy
title_short	T cell landscape and dynamics in immunoglobulin light chain amyloidosis before and after daratumumab‐based therapy
title_full	T cell landscape and dynamics in immunoglobulin light chain amyloidosis before and after daratumumab‐based therapy
title_fullStr	T cell landscape and dynamics in immunoglobulin light chain amyloidosis before and after daratumumab‐based therapy
title_full_unstemmed	T cell landscape and dynamics in immunoglobulin light chain amyloidosis before and after daratumumab‐based therapy
title_sort	t cell landscape and dynamics in immunoglobulin light chain amyloidosis before and after daratumumab‐based therapy
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/b2b678204e184ca281d2bd9be93f879a
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_version_	1718406768167485440

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

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