Ladányi Andrea, Somlai Beáta, Gilde Katalin, Fejös Zsuzsanna, Gaudi István, Tímár József
Department of Tumor Progression, National Institute of Oncology, Semmelweis University, Budapest, Hungary.
Clin Cancer Res. 2004 Jan 15;10(2):521-30. doi: 10.1158/1078-0432.ccr-1161-03.
The central role of T cells in antitumor immunity is well established. However, tumor progression, often seen in the presence of substantial lymphocytic infiltration, suggests that these T cells are not capable of mounting an effective immune response to control tumor growth. Evidence has accumulated that T lymphocytes infiltrating human neoplasms are functionally defective, incompletely activated, or anergic. Therefore, when characterizing the immune competent cells within lymphoid infiltrates of tumors, it is important to assess their activation state. We investigated the expression of two T-cell activation markers, interleukin 2 receptor alpha (CD25) and OX40 (CD134), by immunohistochemistry in primary cutaneous melanoma samples of 76 patients and analyzed it in relation to tumor stage and tumor progression (>5 years follow-up), as well as to patients' survival. We found that the degree of infiltration by CD25(+) and intratumoral OX40(+) lymphocytes showed a tendency to decrease in thicker melanomas. The frequency of samples with high numbers of peritumoral CD25(+) and OX40(+) cells was significantly lower (P = 0.0009 and P = 0.0087, respectively) in melanomas developing distant visceral metastases, compared with nonmetastatic or lymph node metastatic tumors. For both activation markers studied, high peritumoral densities were associated with longer survival by univariate analysis (P = 0.0028 and P = 0.0255 for CD25 and OX40, respectively), whereas peritumoral OX40(+) lymphocyte infiltration had an impact on survival also in multivariate analysis (P = 0.035). The results suggest that the presence of lymphocytes expressing the T-cell activation markers CD25 or OX40 shows correlation with tumor progression as well as with patients' survival in cutaneous malignant melanoma.
T细胞在抗肿瘤免疫中的核心作用已得到充分证实。然而，在大量淋巴细胞浸润的情况下仍常出现肿瘤进展，这表明这些T细胞无法产生有效的免疫反应来控制肿瘤生长。越来越多的证据表明，浸润人类肿瘤的T淋巴细胞存在功能缺陷、激活不完全或无反应性。因此，在表征肿瘤淋巴浸润内的免疫活性细胞时，评估其激活状态很重要。我们通过免疫组织化学研究了76例原发性皮肤黑色素瘤样本中两种T细胞激活标志物白细胞介素2受体α（CD25）和OX40（CD134）的表达，并分析了其与肿瘤分期、肿瘤进展（随访>5年）以及患者生存率的关系。我们发现，在较厚的黑色素瘤中，CD25(+)和肿瘤内OX40(+)淋巴细胞的浸润程度呈下降趋势。与非转移性或淋巴结转移性肿瘤相比，发生远处内脏转移的黑色素瘤中，瘤周CD25(+)和OX40(+)细胞数量较多的样本频率显著更低（分别为P = 0.0009和P = 0.0087）。单因素分析显示，对于所研究 的两种激活标志物，瘤周高密度均与更长的生存期相关（CD25和OX40分别为P = 0.0028和P = 0.0255），而多因素分析中瘤周OX40(+)淋巴细胞浸润也对生存率有影响（P = 0.035）。结果表明，表达T细胞激活标志物CD25或OX40的淋巴细胞的存在与皮肤恶性黑色素瘤的肿瘤进展以及患者生存率相关。
