Coordinated immune networks in leukemia bone marrow microenvironments distinguish response to cellular therapy

IF 17.6 1区医学 Q1 IMMUNOLOGY Science Immunology Pub Date : 2025-01-24 DOI:10.1126/sciimmunol.adr0782

Katie Maurer, Cameron Y. Park, Shouvik Mani, Mehdi Borji, Florian Raths, Kenneth H. Gouin, Livius Penter, Yinuo Jin, Jia Yi Zhang, Crystal Shin, James R. Brenner, Jackson Southard, Sachi Krishna, Wesley Lu, Haoxiang Lyu, Domenic Abbondanza, Chanell Mangum, Lars Rønn Olsen, Michael J. Lawson, Martin Fabani, Donna S. Neuberg, Pavan Bachireddy, Eli N. Glezer, Samouil L. Farhi, Shuqiang Li, Kenneth J. Livak, Jerome Ritz, Robert J. Soiffer, Catherine J. Wu, Elham Azizi

{"title":"Coordinated immune networks in leukemia bone marrow microenvironments distinguish response to cellular therapy","authors":"Katie Maurer, Cameron Y. Park, Shouvik Mani, Mehdi Borji, Florian Raths, Kenneth H. Gouin, Livius Penter, Yinuo Jin, Jia Yi Zhang, Crystal Shin, James R. Brenner, Jackson Southard, Sachi Krishna, Wesley Lu, Haoxiang Lyu, Domenic Abbondanza, Chanell Mangum, Lars Rønn Olsen, Michael J. Lawson, Martin Fabani, Donna S. Neuberg, Pavan Bachireddy, Eli N. Glezer, Samouil L. Farhi, Shuqiang Li, Kenneth J. Livak, Jerome Ritz, Robert J. Soiffer, Catherine J. Wu, Elham Azizi","doi":"10.1126/sciimmunol.adr0782","DOIUrl":null,"url":null,"abstract":"Understanding how intratumoral immune populations coordinate antitumor responses after therapy can guide treatment prioritization. We systematically analyzed an established immunotherapy, donor lymphocyte infusion (DLI), by assessing 348,905 single-cell transcriptomes from 74 longitudinal bone marrow samples of 25 patients with relapsed leukemia; a subset was evaluated by both protein- and transcriptome-based spatial analysis. In acute myeloid leukemia (AML) DLI responders, we identified clonally expanded ZNF683 + CD8 + cytotoxic T lymphocytes with in vitro specificity for patient-matched AML. These cells originated primarily from the DLI product and appeared to coordinate antitumor immune responses through interaction with diverse immune cell types within the marrow microenvironment. Nonresponders lacked this cross-talk and had cytotoxic T lymphocytes with elevated TIGIT expression. Our study identifies recipient bone marrow microenvironment differences as a determinant of an effective antileukemia response and opens opportunities to modulate cellular therapy.","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"22 1","pages":""},"PeriodicalIF":17.6000,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Science Immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1126/sciimmunol.adr0782","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Understanding how intratumoral immune populations coordinate antitumor responses after therapy can guide treatment prioritization. We systematically analyzed an established immunotherapy, donor lymphocyte infusion (DLI), by assessing 348,905 single-cell transcriptomes from 74 longitudinal bone marrow samples of 25 patients with relapsed leukemia; a subset was evaluated by both protein- and transcriptome-based spatial analysis. In acute myeloid leukemia (AML) DLI responders, we identified clonally expanded ZNF683 + CD8 + cytotoxic T lymphocytes with in vitro specificity for patient-matched AML. These cells originated primarily from the DLI product and appeared to coordinate antitumor immune responses through interaction with diverse immune cell types within the marrow microenvironment. Nonresponders lacked this cross-talk and had cytotoxic T lymphocytes with elevated TIGIT expression. Our study identifies recipient bone marrow microenvironment differences as a determinant of an effective antileukemia response and opens opportunities to modulate cellular therapy.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

求助全文

约1分钟内获得全文去求助

来源期刊

Science Immunology Immunology and Microbiology-Immunology

CiteScore

32.90

自引率

2.00%

发文量

183

期刊介绍： Science Immunology is a peer-reviewed journal that publishes original research articles in the field of immunology. The journal encourages the submission of research findings from all areas of immunology, including studies on innate and adaptive immunity, immune cell development and differentiation, immunogenomics, systems immunology, structural immunology, antigen presentation, immunometabolism, and mucosal immunology. Additionally, the journal covers research on immune contributions to health and disease, such as host defense, inflammation, cancer immunology, autoimmunity, allergy, transplantation, and immunodeficiency. Science Immunology maintains the same high-quality standard as other journals in the Science family and aims to facilitate understanding of the immune system by showcasing innovative advances in immunology research from all organisms and model systems, including humans.