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Lack of granzyme expression in T lymphocytes indicates poor cytotoxic T lymphocyte activation in human papillomavirus-associated cervical carcinomas
  1. F. V. CROMME,
  4. M. J. STUKART,
  5. T. D. DE GRUIJL,
  6. J. A. KUMMER,
  7. A. M. LEONHART,
  8. C. J.L.M. MEIJER and
  1. Institute for Pathology, Section of Molecular Pathology, and *Department of Gynecology and Obstetrics, Free University Hospital, Amsterdam, the Netherlands
  1. Address for correspondence: Dr J. M. M. Walboomers, Free University Hospital, Institute for Pathology, Section of Molecular Pathology, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands.


Changes in major histocompatibility complex (MHC) class I expression in neoplastic cells are frequently observed in human papillomavirus type 16 (HPV16)-associated cervical carcinomas. In order to investigate whether this affects cytotoxic T-cell (CTL) activation, 20 HPV16-positive cervical carcinomas with variable MHC expression were analyzed immunohistochemically for the expression of granzyme B and interleukin-2 receptor (IL-2R). The results revealed that most carcinomas show strong CD3+ T-lymphocyte infiltrates. In nine of these cases CD8+ cells outnumbered the CD4+ cells, whereas in the remaining cases equal amounts of CD4+ and CD8+ cells were found. Double staining revealed that CD3+ granzyme B+ cells were not detected in 19 out of 20 cervical lesions, whereas in one carcinoma an occasional cluster of granzyme B+ T cells was observed. Positive controls, including genital warts and renal allograft rejections, showed granzyme B+ T cells. In agreement with this observation was the extremely low frequency of IL-2R+ T cells in the carcinomas tested, while warts contained IL-2R+ lymphocytes. The data indicate that cytotoxic (CD8+) T cells in cervical carcinomas are not activated, as demonstrated by the lack of granzyme B and IL-2R expression in the T cells.

  • cervical carcinoma
  • cytotoxic T lymphocytes
  • granzyme
  • human papillomavirus type 16
  • MHC-I

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