| Abstract: |
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+ na & iuml;ve 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 (AD - [El Daker, Sary; Beqaj, Samida; Boiocchi, Leonardo; Baik, Jeeyeon; Zhu, Menglei; Dogan, Ahmet; Roshal, Mikhail; Galera, Pallavi] Mem Sloan Kettering Canc Ctr, ImCORE Network, Dept Pathol & Lab Med, Hematopathol Serv, New York, NY 10065 USA; [Qualls, David; Salles, Gilles] Mem Sloan Kettering Canc Ctr, Dept Med, Lymphoma Serv, New York, NY USA; [Derkach, Andriy; Seshan, Venkatraman] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY USA |
