High numbers of granzyme B/CD8-positive tumour-infiltrating lymphocytes in nasopharyngeal carcinoma biopsies predict rapid fatal outcome in patients treated with curative intent

Joost J Oudejans, Hari Harijadi, J Alain Kummer, I Bing Tan, Elizabeth Bloemena, Jaap M Middeldorp, Belinda Bladergroen, Danny F Dukers, Wim Vos, Chris J L M Meijer

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58 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)468-75
Number of pages8
JournalJournal of pathology
Issue number4
Publication statusPublished - Dec 2002


  • Adult
  • Biomarkers, Tumor
  • Biopsy
  • CD8 Antigens
  • Disease-Free Survival
  • Female
  • Granzymes
  • Histocompatibility Antigens Class I
  • Humans
  • Journal Article
  • Lymphocytes, Tumor-Infiltrating
  • Male
  • Middle Aged
  • Nasopharyngeal Neoplasms
  • Neoplasm Proteins
  • Prognosis
  • Proportional Hazards Models
  • Research Support, Non-U.S. Gov't
  • Serine Endopeptidases
  • Serpins
  • Survival Rate

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