title: Distribution, function, and prognostic value of cytotoxic T lymphocytes in follicular lymphoma: a 3-D tissue-imaging study.
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.
authors.affiliation: INSERM U1043, Centre de Physiopathologie de Toulouse Purpan, Section Dynamique Moléculaire des Interactions Lymphocytaires, Toulouse, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Laurent
authors.forename: Sabina
authors.initials: S
authors.lastname: Müller
authors.forename: Catherine
authors.initials: C
authors.lastname: Do
authors.forename: Talal
authors.initials: T
authors.lastname: Al-Saati
authors.forename: Sophie
authors.initials: S
authors.lastname: Allart
authors.forename: Luigi Maria
authors.initials: LM
authors.lastname: Larocca
authors.forename: Stefan
authors.initials: S
authors.lastname: Hohaus
authors.forename: Sophie
authors.initials: S
authors.lastname: Duchez
authors.forename: Anne
authors.initials: A
authors.lastname: Quillet-Mary
authors.forename: Guy
authors.initials: G
authors.lastname: Laurent
authors.forename: Pierre
authors.initials: P
authors.lastname: Brousset
authors.forename: Salvatore
authors.initials: S
authors.lastname: Valitutti
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D053804:Granzymes / Q000378:metabolism; D006801:Humans; D021621:Imaging, Three-Dimensional; D008198:Lymph Nodes / Q000473:pathology*; D008224:Lymphoma, Follicular / Q000188:drug therapy / Q000453:epidemiology* / Q000473:pathology*; D008297:Male; D018613:Microscopy, Confocal / Q000379:methods; D008875:Middle Aged; D011237:Predictive Value of Tests; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D012307:Risk Factors; D000069283:Rituximab; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism / Q000473:pathology*; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D014408:Biomarkers, Tumor; D017252:CD3 Complex; D016827:CD8 Antigens; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D053804:Granzymes; D011241:Prednisone