title: High numbers of granzyme B/CD8-positive tumour-infiltrating lymphocytes in nasopharyngeal carcinoma biopsies predict rapid fatal outcome in patients treated with curative intent.
abstract: This study determined whether tumour-infiltrating lymphocytes (TILs) in nasopharyngeal carcinomas (NPCs) include activated cytotoxic T lymphocytes (CTLs) and whether the numbers of activated CTLs in these biopsies are related to clinical outcome. Moreover, the study investigated whether the numbers of activated CTLs are associated with the expression of MHC class I proteins and the granzyme B antagonist PI-9 in the tumour cells. Forty-three Indonesian NPC patients (T(1-3), N(1-3), M(0)), who were treated with curative intent by radiotherapy only, were studied. Tumour-infiltrating activated CTLs were detected using antibodies against granzyme B, CD8, and CD56. Expression of MHC class I proteins and PI-9 was also determined by immunohistochemistry. Granzyme B-positive TILs were detected in all NPC biopsies. The presence of a high percentage (>25%) of granzyme B-positive TILs appeared to be a very strong predictor of a rapid fatal clinical outcome, independent of stage. Complete absence of MHC class I heavy chain expression in tumour cells was observed in 11 of 31 evaluable cases and low levels were observed in seven additional cases. No association between MHC class I expression and the numbers of granzyme B-positive TILs was observed. Expression of the granzyme B antagonist PI-9 in tumour cells was detected in three cases. It is concluded that the presence of many granzyme B-positive TILs in a selected group of Indonesian NPC patients is a strong and stage-independent marker for a rapid fatal clinical outcome.
authors.affiliation: Department of Pathology, VU Medical Center, Amsterdam, The Netherlands. jj.oudejans@vumc.nl
authors.forename: Joost J
authors.initials: JJ
authors.lastname: Oudejans
authors.forename: Hari
authors.initials: H
authors.lastname: Harijadi
authors.forename: J Alain
authors.initials: JA
authors.lastname: Kummer
authors.forename: I Bing
authors.initials: IB
authors.lastname: Tan
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Bloemena
authors.forename: Jaap M
authors.initials: JM
authors.lastname: Middeldorp
authors.forename: Belinda
authors.initials: B
authors.lastname: Bladergroen
authors.forename: Danny F
authors.initials: DF
authors.lastname: Dukers
authors.forename: Wim
authors.initials: W
authors.lastname: Vos
authors.forename: Chris J L M
authors.initials: CJ
authors.lastname: Meijer
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D016827:CD8 Antigens / Q000032:analysis*; D018572:Disease-Free Survival; D005260:Female; D053804:Granzymes; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism; D011379:Prognosis; D016016:Proportional Hazards Models; D012697:Serine Endopeptidases / Q000032:analysis*; D015843:Serpins / Q000378:metabolism; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I; D009363:Neoplasm Proteins; C102316:SERPINB9 protein, human; D015843:Serpins; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases