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-cel...
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| Format: | Article |
| Language: | English |
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Ferrata Storti Foundation
2025-02-01
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| Series: | Haematologica |
| Online Access: | https://haematologica.org/article/view/11931 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Sary El Daker |
| collection | DOAJ |
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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+ naive 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 (Treg) 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 ( |
| format | Article |
| id | doaj-art-67bf09369d4b45d8a2321b2a52282003 |
| institution | Kabale University |
| issn | 0390-6078 1592-8721 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Ferrata Storti Foundation |
| record_format | Article |
| series | Haematologica |
| spelling | doaj-art-67bf09369d4b45d8a2321b2a522820032025-02-06T19:45:06ZengFerrata Storti FoundationHaematologica0390-60781592-87212025-02-01999110.3324/haematol.2024.286383Deep immunophenotypic dissection and clinical impact of T cells in the follicular lymphoma microenvironmentSary El Daker0David Qualls1Andriy Derkach2Samida Beqaj3Leonardo Boiocchi4Venkatraman Seshan5Jeeyeon Baik6Menglei Zhu7Gilles Salles8Ahmet Dogan9Mikhail Roshal10Pallavi Galera11Hematopathology Service, Department of Pathology and Laboratory MedicineLymphoma Service, Department of MedicineDepartment of Epidemiology and BiostatisticsHematopathology Service, Department of Pathology and Laboratory MedicineHematopathology Service, Department of Pathology and Laboratory MedicineDepartment of Epidemiology and BiostatisticsHematopathology Service, Department of Pathology and Laboratory MedicineHematopathology Service, Department of Pathology and Laboratory MedicineLymphoma Service, Department of MedicineHematopathology Service, Department of Pathology and Laboratory MedicineHematopathology Service, Department of Pathology and Laboratory MedicineHematopathology Service, Department of Pathology and Laboratory Medicine 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+ naive 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 (Treg) 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 (https://haematologica.org/article/view/11931 |
| spellingShingle | 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 Deep immunophenotypic dissection and clinical impact of T cells in the follicular lymphoma microenvironment Haematologica |
| title | Deep immunophenotypic dissection and clinical impact of T cells in the follicular lymphoma microenvironment |
| title_full | Deep immunophenotypic dissection and clinical impact of T cells in the follicular lymphoma microenvironment |
| title_fullStr | Deep immunophenotypic dissection and clinical impact of T cells in the follicular lymphoma microenvironment |
| title_full_unstemmed | Deep immunophenotypic dissection and clinical impact of T cells in the follicular lymphoma microenvironment |
| title_short | Deep immunophenotypic dissection and clinical impact of T cells in the follicular lymphoma microenvironment |
| title_sort | deep immunophenotypic dissection and clinical impact of t cells in the follicular lymphoma microenvironment |
| url | https://haematologica.org/article/view/11931 |
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