title: Abundant expression of interleukin-21 receptor in follicular lymphoma cells is associated with more aggressive disease.
abstract: Recombinant interleukin-21 (IL-21) has potential utility in cancer therapy. Stimulation with IL-21 can induce apoptosis in follicular lymphoma (FL) cells, and existing studies have suggested that IL-21 signaling may function in tumor suppression. In order to elucidate the relationship between IL-21 receptor (IL-21R) expression and clinical and pathological features in FL, IL-21R was quantified in 114 pretreatment biopsy samples using either conventional immunohistochemistry or immunofluorescence microscopy and automated quantitative analysis (AQUA). Reduced expression of IL-21R was associated with favorable overall survival (p = 0.048). AQUA analysis showed an association with the presence of diffuse large B-cell lymphoma (DLBCL) in the biopsy sample (p = 0.03), and expression of IL-21R was up-regulated upon transformation of FL to DLBCL in two cases. Our results based on the largest survey to date raise the possibility that IL-21 signaling in FL cells, rather than being tumor suppressive, supports tumor progression and that therapeutic benefit could be realized by blocking IL-21R instead of stimulating it.
authors.affiliation: Department of Pathology and Molecular Medicine, Queen's University, Kingston, Ontario, Canada.
authors.forename: Brianne
authors.initials: B
authors.lastname: Wood
authors.forename: Soma
authors.initials: S
authors.lastname: Sikdar
authors.forename: Suk Jin
authors.initials: SJ
authors.lastname: Choi
authors.forename: Shakeel
authors.initials: S
authors.lastname: Virk
authors.forename: Abdulmohsen
authors.initials: A
authors.lastname: Alhejaily
authors.forename: Tara
authors.initials: T
authors.lastname: Baetz
authors.forename: David P
authors.initials: DP
authors.lastname: LeBrun
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008221:Lymphoid Tissue / Q000378:metabolism / Q000473:pathology; D008224:Lymphoma, Follicular / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D053655:Receptors, Interleukin-21 / Q000235:genetics / Q000378:metabolism*
chemical_list: D053655:Receptors, Interleukin-21