The tumour microenvironment influences survival and time to transformation in follicular lymphoma in the rituximab era.
Yngvild Nuvin Blaker,Yngvild Nuvin Blaker,Signe Spetalen,Marianne Brodtkorb,Marianne Brodtkorb,Ole Christian Lingjærde,Klaus Beiske,Bjørn Østenstad,Birgitta Sander,Björn E. Wahlin,Christopher Michael Melen,June Helen Myklebust,June Helen Myklebust,Harald Holte,Harald Holte,Jan Delabie,Erlend B. Smeland,Erlend B. Smeland +17 more
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Better developed CD21+ follicular dendritic cell (FDC) meshworks at diagnosis was a negative prognostic factor for overall survival, progression‐free survival (PFS) and time to transformation (TTT) in patients with subsequently transformed FL.Abstract:
The tumour microenvironment influences outcome in patients with follicular lymphoma (FL), but its impact on transformation is less studied. We investigated the prognostic significance of the tumour microenvironment on transformation and survival in FL patients treated in the rituximab era. We examined diagnostic and transformed biopsies from 52 FL patients using antibodies against CD3, CD4, CD8, CD21 (CR2), CD57 (B3GAT1), CD68, FOXP3, TIA1, PD-1 (PDCD1), PD-L1 (CD274) and PAX5. Results were compared with a second cohort of 40 FL patients without signs of transformation during a minimum of five years observation time. Cell numbers and localization were semi-quantitatively assessed. Better developed CD21+ follicular dendritic cell (FDC) meshworks at diagnosis was a negative prognostic factor for overall survival (OS), progression-free survival (PFS) and time to transformation (TTT) in patients with subsequently transformed FL. Remnants of FDC meshworks at transformation were associated with shorter OS and PFS from transformation. High degrees of intrafollicular CD68+ and PD-L1+ macrophage infiltration, high total area scores and an extrafollicular/diffuse pattern of FOXP3+ T cells and high intrafollicular scores of CD4+ T cells at diagnosis were associated with shorter TTT. Scores of several T-cell subset markers from the combined patient cohorts were predictive for transformation, especially CD4 and CD57.read more
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PD-1 expression and clinical PD-1 blockade in B-cell lymphomas.
TL;DR: Mechanisms and predictive biomarkers for PD-1 blockade immunotherapy, treatment-related adverse events, hyperprogression, and combination therapies are discussed in the context of B-cell lymphomas.
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High rate of durable complete remission in follicular lymphoma after CD19 CAR-T cell immunotherapy
Alexandre V. Hirayama,Jordan Gauthier,Kevin A. Hay,Kevin A. Hay,Jenna M. Voutsinas,Qian Wu,Barbara S. Pender,Reed M. Hawkins,Aesha Vakil,Rachel N. Steinmetz,Stanley R. Riddell,Stanley R. Riddell,David G. Maloney,David G. Maloney,Cameron J. Turtle,Cameron J. Turtle +15 more
TL;DR: CD19 CAR-T cell immunotherapy is highly effective in adults with clinically aggressive R/R follicular lymphoma with or without transformation, with durable remission in a high proportion of FL patients.
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Chromatin modifying gene mutations in follicular lymphoma.
TL;DR: The current state of knowledge on CMG mutations in FL is reviewed, their potential as therapeutic targets are discussed, and the perspective on unexplored areas that should be considered in the future is offered.
Journal ArticleDOI
Total metabolic tumor volume, circulating tumor cells, cell-free DNA: distinct prognostic value in follicular lymphoma.
Marie-Hélène Delfau-Larue,Axel Van Der Gucht,Jehan Dupuis,Jean-Philippe Jais,Isabelle Nel,Asma Beldi-Ferchiou,Salma Hamdane,Ichrafe Benmaad,Gaelle Laboure,Benjamin Verret,Corinne Haioun,Christiane Copie-Bergman,Alina Berriolo-Riedinger,Philippine Robert,René-Olivier Casasnovas,E. Itti +15 more
TL;DR: CTCs and cfDNA correlate with TMTV in FL, and all 3 influence patient outcome, suggesting that these parameters provide relevant information for tumor-tailored therapy.
Journal ArticleDOI
Can histologic transformation of follicular lymphoma be predicted and prevented
TL;DR: Whether evidence exists in the literature that transformation might be prevented altogether, based on the choice of therapy for follicular lymphoma patients, is assessed.
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Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells
Sandeep S. Dave,George E. Wright,Bruce K. Tan,Andreas Rosenwald,Andreas Rosenwald,Randy D. Gascoyne,Wing C. Chan,Richard I. Fisher,Rita M. Braziel,Lisa M. Rimsza,Thomas M. Grogan,Thomas P. Miller,Michael LeBlanc,Timothy C. Greiner,Dennis D. Weisenburger,James C. Lynch,Julie M. Vose,James O. Armitage,Erlend B. Smeland,Stein Kvaløy,Harald Holte,Jan Delabie,Joseph M. Connors,Peter M. Lansdorp,Qin Ouyang,T. Andrew Lister,Andrew Davies,Andrew J. Norton,H. Konrad Muller-Hermelink,German Ott,Elias Campo,Emilio Montserrat,Wyndham H. Wilson,Elaine S. Jaffe,Richard M. Simon,Liming Yang,John Powell,Hong Zhao,Neta Goldschmidt,Michael Chiorazzi,Louis M. Staudt +40 more
TL;DR: The length of survival among patients with follicular lymphoma correlates with the molecular features of nonmalignant immune cells present in the tumor at diagnosis.
Journal ArticleDOI
Mechanisms of suppression by suppressor T cells
TL;DR: The mechanisms of suppression, which include the local secretion of cytokines such as TGF-β and direct cell contact through binding of cell surface molecules such as CTLA-4 on suppressor T cells to CD80 and CD86 molecules on effector Tcells, are discussed.
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