Berit Müller-Meinhard, Nicole Seifert, Johanna Grund, Sarah Reinke, Fatih Yalcin, Helen Kaul, Sven Borchmann, Bastian von Tresckow, Peter Borchmann, Annette Plütschow, Julia Richter, Andreas Engert, Michael Altenbuchinger, Paul J. Bröckelmann, Wolfram Klapper
{"title":"霍奇金-里德-斯登堡细胞上人类白细胞抗原(HLA)Ⅰ类的表达是典型霍奇金淋巴瘤微环境组成的主要决定因素,与 EBV 无关","authors":"Berit Müller-Meinhard, Nicole Seifert, Johanna Grund, Sarah Reinke, Fatih Yalcin, Helen Kaul, Sven Borchmann, Bastian von Tresckow, Peter Borchmann, Annette Plütschow, Julia Richter, Andreas Engert, Michael Altenbuchinger, Paul J. Bröckelmann, Wolfram Klapper","doi":"10.1002/hem3.84","DOIUrl":null,"url":null,"abstract":"<p>Hodgkin–Reed–Sternberg cells (HRSCs) in classic Hodgkin Lymphoma (HL) frequently lack expression of human leukocyte antigen class I (HLA-I), considered to hamper activation of cytotoxic T cells in the tumor microenvironment (TME). Here, we demonstrate HLA-I expression on HRSCs to be a strong determinant of TME composition whereas expression of HLA-II was associated with only minor differential gene expression in the TME. In HLA-I-positive HL the HRSC content and expression of CCL17/TARC in HRSCs are low, independent of the presence of Epstein–Barr virus in HRSCs. Additionally, HLA-I-positive HL shows a high content of CD8+ cytotoxic T cells. However, an increased expression of the inhibitory immune checkpoint LAG3 on CD8+ T cells in close proximity to HRSCs is observed. Suggesting interference with cytotoxic activity, we observed an absence of clonally expanded T cells in the TME. While HLA-I-positive HL is not associated with an unfavorable clinical course in our cohorts, they share features with the recently described H2 subtype of HL. Given the major differences in TME composition, immune checkpoint inhibitors may differ in their mechanism of action in HLA-I-positive compared to HLA-I-negative HL.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"8 6","pages":""},"PeriodicalIF":7.6000,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.84","citationCount":"0","resultStr":"{\"title\":\"Human leukocyte antigen (HLA) class I expression on Hodgkin–Reed–Sternberg cells is an EBV-independent major determinant of microenvironment composition in classic Hodgkin lymphoma\",\"authors\":\"Berit Müller-Meinhard, Nicole Seifert, Johanna Grund, Sarah Reinke, Fatih Yalcin, Helen Kaul, Sven Borchmann, Bastian von Tresckow, Peter Borchmann, Annette Plütschow, Julia Richter, Andreas Engert, Michael Altenbuchinger, Paul J. Bröckelmann, Wolfram Klapper\",\"doi\":\"10.1002/hem3.84\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Hodgkin–Reed–Sternberg cells (HRSCs) in classic Hodgkin Lymphoma (HL) frequently lack expression of human leukocyte antigen class I (HLA-I), considered to hamper activation of cytotoxic T cells in the tumor microenvironment (TME). Here, we demonstrate HLA-I expression on HRSCs to be a strong determinant of TME composition whereas expression of HLA-II was associated with only minor differential gene expression in the TME. In HLA-I-positive HL the HRSC content and expression of CCL17/TARC in HRSCs are low, independent of the presence of Epstein–Barr virus in HRSCs. Additionally, HLA-I-positive HL shows a high content of CD8+ cytotoxic T cells. However, an increased expression of the inhibitory immune checkpoint LAG3 on CD8+ T cells in close proximity to HRSCs is observed. Suggesting interference with cytotoxic activity, we observed an absence of clonally expanded T cells in the TME. While HLA-I-positive HL is not associated with an unfavorable clinical course in our cohorts, they share features with the recently described H2 subtype of HL. Given the major differences in TME composition, immune checkpoint inhibitors may differ in their mechanism of action in HLA-I-positive compared to HLA-I-negative HL.</p>\",\"PeriodicalId\":12982,\"journal\":{\"name\":\"HemaSphere\",\"volume\":\"8 6\",\"pages\":\"\"},\"PeriodicalIF\":7.6000,\"publicationDate\":\"2024-06-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.84\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"HemaSphere\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/hem3.84\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"HemaSphere","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/hem3.84","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"HEMATOLOGY","Score":null,"Total":0}
Human leukocyte antigen (HLA) class I expression on Hodgkin–Reed–Sternberg cells is an EBV-independent major determinant of microenvironment composition in classic Hodgkin lymphoma
Hodgkin–Reed–Sternberg cells (HRSCs) in classic Hodgkin Lymphoma (HL) frequently lack expression of human leukocyte antigen class I (HLA-I), considered to hamper activation of cytotoxic T cells in the tumor microenvironment (TME). Here, we demonstrate HLA-I expression on HRSCs to be a strong determinant of TME composition whereas expression of HLA-II was associated with only minor differential gene expression in the TME. In HLA-I-positive HL the HRSC content and expression of CCL17/TARC in HRSCs are low, independent of the presence of Epstein–Barr virus in HRSCs. Additionally, HLA-I-positive HL shows a high content of CD8+ cytotoxic T cells. However, an increased expression of the inhibitory immune checkpoint LAG3 on CD8+ T cells in close proximity to HRSCs is observed. Suggesting interference with cytotoxic activity, we observed an absence of clonally expanded T cells in the TME. While HLA-I-positive HL is not associated with an unfavorable clinical course in our cohorts, they share features with the recently described H2 subtype of HL. Given the major differences in TME composition, immune checkpoint inhibitors may differ in their mechanism of action in HLA-I-positive compared to HLA-I-negative HL.
期刊介绍:
HemaSphere, as a publication, is dedicated to disseminating the outcomes of profoundly pertinent basic, translational, and clinical research endeavors within the field of hematology. The journal actively seeks robust studies that unveil novel discoveries with significant ramifications for hematology.
In addition to original research, HemaSphere features review articles and guideline articles that furnish lucid synopses and discussions of emerging developments, along with recommendations for patient care.
Positioned as the foremost resource in hematology, HemaSphere augments its offerings with specialized sections like HemaTopics and HemaPolicy. These segments engender insightful dialogues covering a spectrum of hematology-related topics, including digestible summaries of pivotal articles, updates on new therapies, deliberations on European policy matters, and other noteworthy news items within the field. Steering the course of HemaSphere are Editor in Chief Jan Cools and Deputy Editor in Chief Claire Harrison, alongside the guidance of an esteemed Editorial Board comprising international luminaries in both research and clinical realms, each representing diverse areas of hematologic expertise.