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High numbers of granzyme B/CD8‐positive tumour‐infiltrating lymphocytes in nasopharyngeal carcinoma biopsies predict rapid fatal outcome in patients treated with curative intent
Author(s) -
Oudejans Joost J,
Harijadi Hari,
Kummer J Alain,
Tan I Bing,
Bloemena Elizabeth,
Middeldorp Jaap M,
Bladergroen Belinda,
Dukers Danny F,
Vos Wim,
Meijer Chris JLM
Publication year - 2002
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.1236
Subject(s) - granzyme b , granzyme , cytotoxic t cell , cd8 , tumor infiltrating lymphocytes , nasopharyngeal carcinoma , immunohistochemistry , medicine , mhc class i , immunology , mhc class ii , pathology , biology , cancer research , major histocompatibility complex , radiation therapy , antigen , perforin , biochemistry , in vitro
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. Copyright © 2002 John Wiley & Sons, Ltd.