PURPOSE: Previous studies have demonstrated the prognostic importance of the immune microenvironment in follicular lymphoma (FL). To investigate the molecular mechanisms during which tumor-infiltrating T cells (TILs) are altered in the FL microenvironment, we studied highly purified CD4 and CD8 TILs from lymph node biopsies at diagnosis in treatment-naive patients with FL compared with reactive tonsils and the peripheral blood of healthy donors. PATIENTS AND METHODS: Gene expression profiling of highly purified CD4 and CD8 TILs was performed on the Affymetrix platform. Diagnostic tissue microarrays from an independent patient set (n = 172) were used to verify protein expression and analyze any impact of TIL-expressed genes on outcome. Time-lapse imaging was used to assess T-cell motility. RESULTS: The most upregulated genes in both CD4 and CD8 TILs were PMCH, ETV1, and TNFRSF9. PMCH is not expressed in peripheral blood T cells, but expression is highly induced on culture with FL. Both CD4 and CD8 TILs from patients with FL have significantly impaired motility compared with those of healthy TILs from reactive tonsils and this can be induced on healthy T cells by FL cells. During multivariate analysis, a model incorporating the number and location of T cells expressing PMCH, NAMPT, and ETV1 showed prognostic significance for overall survival and for time to transformation. CONCLUSION: We showed altered gene expression in TILs in FL and demonstrated that altering the immune microenvironment in FL affects overall survival and time to transformation in this disease.
PURPOSE: Previous studies have demonstrated the prognostic importance of the immune microenvironment in follicular lymphoma (FL). To investigate the molecular mechanisms during which tumor-infiltrating T cells (TILs) are altered in the FL microenvironment, we studied highly purified CD4 and CD8 TILs from lymph node biopsies at diagnosis in treatment-naive patients with FL compared with reactive tonsils and the peripheral blood of healthy donors. PATIENTS AND METHODS: Gene expression profiling of highly purified CD4 and CD8 TILs was performed on the Affymetrix platform. Diagnostic tissue microarrays from an independent patient set (n = 172) were used to verify protein expression and analyze any impact of TIL-expressed genes on outcome. Time-lapse imaging was used to assess T-cell motility. RESULTS: The most upregulated genes in both CD4 and CD8 TILs were PMCH, ETV1, and TNFRSF9. PMCH is not expressed in peripheral blood T cells, but expression is highly induced on culture with FL. Both CD4 and CD8 TILs from patients with FL have significantly impaired motility compared with those of healthy TILs from reactive tonsils and this can be induced on healthy T cells by FL cells. During multivariate analysis, a model incorporating the number and location of T cells expressing PMCH, NAMPT, and ETV1 showed prognostic significance for overall survival and for time to transformation. CONCLUSION: We showed altered gene expression in TILs in FL and demonstrated that altering the immune microenvironment in FL affects overall survival and time to transformation in this disease.
Authors: Pedro Farinha; Hamid Masoudi; Brian F Skinnider; Karey Shumansky; John J Spinelli; Karamjit Gill; Richard Klasa; Nicolas Voss; Joseph M Connors; Randy D Gascoyne Journal: Blood Date: 2005-06-02 Impact factor: 22.113
Authors: Joram D Mul; Chun-Xia Yi; Sjoerd A A van den Berg; Marieke Ruiter; Pim W Toonen; Martine C J van der Elst; Peter J Voshol; Bart A Ellenbroek; Andries Kalsbeek; Susanne E la Fleur; Edwin Cuppen Journal: Am J Physiol Endocrinol Metab Date: 2009-11-24 Impact factor: 4.310
Authors: Alan G Ramsay; Andrew J Clear; Gavin Kelly; Rewas Fatah; Janet Matthews; Finlay Macdougall; T Andrew Lister; Abigail M Lee; Maria Calaminici; John G Gribben Journal: Blood Date: 2009-09-28 Impact factor: 22.113
Authors: Hilary Sandig; Joanne McDonald; Jane Gilmour; Matthew Arno; Tak H Lee; David J Cousins Journal: Proc Natl Acad Sci U S A Date: 2007-07-18 Impact factor: 11.205
Authors: Nathan H Fowler; Chan Yoon Cheah; Randy D Gascoyne; John Gribben; Sattva S Neelapu; Paolo Ghia; Catherine Bollard; Stephen Ansell; Michael Curran; Wyndham H Wilson; Susan O'Brien; Cliona Grant; Richard Little; Thorsten Zenz; Loretta J Nastoupil; Kieron Dunleavy Journal: Haematologica Date: 2016-05 Impact factor: 9.941
Authors: Veronika Bachanova; Dhifaf Sarhan; Todd E DeFor; Sarah Cooley; Angela Panoskaltsis-Mortari; Bruce R Blazar; Julie M Curtsinger; Linda Burns; Daniel J Weisdorf; Jeffrey S Miller Journal: Cancer Immunol Immunother Date: 2017-12-07 Impact factor: 6.968