Distribution, function, and prognostic value of cytotoxic T lymphocytes in follicular lymphoma: a 3-D tissue-imaging study
Open Access
- 17 November 2011
- journal article
- research article
- Published by American Society of Hematology in Blood
- Vol. 118 (20), 5371-5379
- https://doi.org/10.1182/blood-2011-04-345777
Abstract
CD8+ CTLs are thought to play a role in the control of follicular lymphoma (FL). Yet, the link between CTL tissue distribution, activation status, ability to kill FL cells in vivo, and disease progression is still elusive. Pretreatment lymph nodes from FL patients were analyzed by IHC (n = 80) or by 3-color confocal microscopy (n = 10). IHC revealed a rich infiltrate of CD8+ granzyme B+ (GrzB) cells in FL interfollicular spaces. Accordingly, confocal microscopy showed an increased number of CD3+CD8+GrzB+ CTLs and a brighter GrzB staining in individual CTL in FL samples compared with reactive lymph nodes. CTLs did not penetrate tumor nodules. In 3-dimensional (3-D) image reconstructions, CTLs were detected at the FL follicle border where they formed lytic synapse-like structures with FL B cells and with apoptotic cells, suggesting an in situ cytotoxic function. Finally, although GrzB expression in CTLs did not correlate with risk factors, high GrzB content correlated with prolonged progression free-survival (PFS) after rituximab-combined chemotherapy. Our results show the recruitment of armed CTLs with a tumor-controlling potential into FL lymph nodes and suggest that CTL-associated GrzB expression could influence PFS in FL patients having received rituximab-combined chemotherapy.Keywords
This publication has 32 references indexed in Scilit:
- Prognostic Factors in Follicular LymphomaJournal of Clinical Oncology, 2010
- Rituximab combined with chemotherapy and interferon in follicular lymphoma patients: results of the GELA-GOELAMS FL2000 studyBlood, 2008
- High Numbers of Tumor-Associated Macrophages Have an Adverse Prognostic Value That Can Be Circumvented by Rituximab in Patients With Follicular Lymphoma Enrolled Onto the GELA-GOELAMS FL-2000 TrialJournal of Clinical Oncology, 2008
- Gene-Expression and Immunohistochemical Study of Specific T-Cell Subsets and Accessory Cell Types in the Transformation and Prognosis of Follicular LymphomaJournal of Clinical Oncology, 2007
- Immunohistochemical Patterns of Reactive Microenvironment Are Associated With Clinicobiologic Behavior in Follicular Lymphoma PatientsJournal of Clinical Oncology, 2006
- Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study GroupBlood, 2005
- CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphomaBlood, 2005
- Prediction of Survival in Follicular Lymphoma Based on Molecular Features of Tumor-Infiltrating Immune CellsThe New England Journal of Medicine, 2004
- Follicular Lymphoma International Prognostic IndexBlood, 2004
- Recombinant Interferon Alfa-2b Combined with a Regimen Containing Doxorubicin in Patients with Advanced Follicular LymphomaThe New England Journal of Medicine, 1993