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 J L M
Department of Pathology, VU Medical Center, Amsterdam, The Netherlands.
J Pathol. 2002 Dec;198(4):468-75. doi: 10.1002/path.1236.
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.
本研究确定了鼻咽癌(NPC)中的肿瘤浸润淋巴细胞(TIL)是否包括活化的细胞毒性T淋巴细胞(CTL),以及这些活检组织中活化CTL的数量是否与临床结局相关。此外,该研究还调查了活化CTL的数量是否与肿瘤细胞中MHC I类蛋白和颗粒酶B拮抗剂PI-9的表达有关。对43例仅接受根治性放疗的印度尼西亚NPC患者(T(1 - 3),N(1 - 3),M(0))进行了研究。使用抗颗粒酶B、CD8和CD56的抗体检测肿瘤浸润活化CTL。通过免疫组织化学法测定MHC I类蛋白和PI-9的表达。在所有NPC活检组织中均检测到颗粒酶B阳性TIL。颗粒酶B阳性TIL的高百分比(>25%)的存在似乎是快速致命临床结局的一个非常强的预测指标,与分期无关。在31例可评估病例中的11例中观察到肿瘤细胞完全缺乏MHC I类重链表达,另外7例中观察到低水平表达。未观察到MHC I类表达与颗粒酶B阳性TIL数量之间的关联。在3例中检测到肿瘤细胞中颗粒酶B拮抗剂PI-9的表达。结论是,在一组选定的印度尼西亚NPC患者中,许多颗粒酶B阳性TIL的存在是快速致命临床结局的一个强有力且与分期无关的标志物。