Sary El Daker, David Qualls, Andriy Derkach, Samida Beqaj, Leonardo Boiocchi, Venkatraman Seshan, Jeeyeon Baik, Menglei Zhu, Gilles Salles, Ahmet Dogan, Mikhail Roshal, Pallavi Galera
{"title":"滤泡性淋巴瘤微环境中T细胞的深度免疫表型解剖及临床影响。","authors":"Sary El Daker, David Qualls, Andriy Derkach, Samida Beqaj, Leonardo Boiocchi, Venkatraman Seshan, Jeeyeon Baik, Menglei Zhu, Gilles Salles, Ahmet Dogan, Mikhail Roshal, Pallavi Galera","doi":"10.3324/haematol.2024.286383","DOIUrl":null,"url":null,"abstract":"<p><p>Follicular lymphoma (FL) is an indolent B-cell lymphoma with a heterogenous disease course, and patients may not require immediate treatment upon diagnosis. Scrutiny of its microenvironment may provide key insights into lymphomagenesis and enhancement of therapeutic options. We analyzed the T-cell composition of a large, well-annotated follicular hyperplasia (FH; N=43) cohort utilizing standardized high dimensionality flow cytometry (>150,000 cells analyzed/sample) and a novel reproducible analytical pipeline leading to identification of even minor T-cell subsets. This baseline reference set was compared to prospectively collected FL samples (N=91) from untreated patients (FL-UT) and patients with relapsed/refractory disease (FL-RR). Compared to FH, both FL-UT and FL-RR specimens exhibited depletion of CD4+ and CD8+ naïve subsets and were characterized by an immune suppressive microenvironment enriched in specific inhibitory T cells, along with exhausted memory T cells overexpressing varying combinations of immune checkpoint receptors. FL specimens showed enrichment of T-follicular regulatory cells (TFR) and two highly suppressive regulatory T-cell (T-reg) populations expressing TIGIT and CTLA4 (TC) and PD1, TIGIT, CTLA4, and TIM3 (PTCTi). FL-UT cases with either increased T-reg TC or increased T-follicular helper cells (TFH) showed reduced time to first treatment (</= 3 months). Our study suggests that changes in the balance between TFR, T-reg and TFH may lead to greater tumor growth and identifies factors that are associated with earlier time to treatment in FL-UT. We also identified specific combinations of immune checkpoint receptors that may be used to target specific inhibitory T-cell subsets and regulatory cells in FL to increase anti-tumor immune response.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"1808-1821"},"PeriodicalIF":8.2000,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12358791/pdf/","citationCount":"0","resultStr":"{\"title\":\"Deep immunophenotypic dissection and clinical impact of T cells in the follicular lymphoma microenvironment.\",\"authors\":\"Sary El Daker, David Qualls, Andriy Derkach, Samida Beqaj, Leonardo Boiocchi, Venkatraman Seshan, Jeeyeon Baik, Menglei Zhu, Gilles Salles, Ahmet Dogan, Mikhail Roshal, Pallavi Galera\",\"doi\":\"10.3324/haematol.2024.286383\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Follicular lymphoma (FL) is an indolent B-cell lymphoma with a heterogenous disease course, and patients may not require immediate treatment upon diagnosis. Scrutiny of its microenvironment may provide key insights into lymphomagenesis and enhancement of therapeutic options. We analyzed the T-cell composition of a large, well-annotated follicular hyperplasia (FH; N=43) cohort utilizing standardized high dimensionality flow cytometry (>150,000 cells analyzed/sample) and a novel reproducible analytical pipeline leading to identification of even minor T-cell subsets. This baseline reference set was compared to prospectively collected FL samples (N=91) from untreated patients (FL-UT) and patients with relapsed/refractory disease (FL-RR). Compared to FH, both FL-UT and FL-RR specimens exhibited depletion of CD4+ and CD8+ naïve subsets and were characterized by an immune suppressive microenvironment enriched in specific inhibitory T cells, along with exhausted memory T cells overexpressing varying combinations of immune checkpoint receptors. FL specimens showed enrichment of T-follicular regulatory cells (TFR) and two highly suppressive regulatory T-cell (T-reg) populations expressing TIGIT and CTLA4 (TC) and PD1, TIGIT, CTLA4, and TIM3 (PTCTi). FL-UT cases with either increased T-reg TC or increased T-follicular helper cells (TFH) showed reduced time to first treatment (</= 3 months). Our study suggests that changes in the balance between TFR, T-reg and TFH may lead to greater tumor growth and identifies factors that are associated with earlier time to treatment in FL-UT. We also identified specific combinations of immune checkpoint receptors that may be used to target specific inhibitory T-cell subsets and regulatory cells in FL to increase anti-tumor immune response.</p>\",\"PeriodicalId\":12964,\"journal\":{\"name\":\"Haematologica\",\"volume\":\" \",\"pages\":\"1808-1821\"},\"PeriodicalIF\":8.2000,\"publicationDate\":\"2025-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12358791/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Haematologica\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3324/haematol.2024.286383\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/2/6 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Haematologica","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3324/haematol.2024.286383","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/2/6 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"HEMATOLOGY","Score":null,"Total":0}
Deep immunophenotypic dissection and clinical impact of T cells in the follicular lymphoma microenvironment.
Follicular lymphoma (FL) is an indolent B-cell lymphoma with a heterogenous disease course, and patients may not require immediate treatment upon diagnosis. Scrutiny of its microenvironment may provide key insights into lymphomagenesis and enhancement of therapeutic options. We analyzed the T-cell composition of a large, well-annotated follicular hyperplasia (FH; N=43) cohort utilizing standardized high dimensionality flow cytometry (>150,000 cells analyzed/sample) and a novel reproducible analytical pipeline leading to identification of even minor T-cell subsets. This baseline reference set was compared to prospectively collected FL samples (N=91) from untreated patients (FL-UT) and patients with relapsed/refractory disease (FL-RR). Compared to FH, both FL-UT and FL-RR specimens exhibited depletion of CD4+ and CD8+ naïve subsets and were characterized by an immune suppressive microenvironment enriched in specific inhibitory T cells, along with exhausted memory T cells overexpressing varying combinations of immune checkpoint receptors. FL specimens showed enrichment of T-follicular regulatory cells (TFR) and two highly suppressive regulatory T-cell (T-reg) populations expressing TIGIT and CTLA4 (TC) and PD1, TIGIT, CTLA4, and TIM3 (PTCTi). FL-UT cases with either increased T-reg TC or increased T-follicular helper cells (TFH) showed reduced time to first treatment (
期刊介绍：
Haematologica is a journal that publishes articles within the broad field of hematology. It reports on novel findings in basic, clinical, and translational research.
Scope:
The scope of the journal includes reporting novel research results that:
Have a significant impact on understanding normal hematology or the development of hematological diseases.
Are likely to bring important changes to the diagnosis or treatment of hematological diseases.
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