PO.IM02.04 · 免疫学
原发性皮肤黑色素瘤中不同类别肿瘤浸润淋巴细胞内的细胞因子表达：一项免疫组织化学研究
Cytokine expression within the different categories of tumor-infiltrating lymphocytes in primary cutaneous melanoma: an immunohistochemical study
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摘要 Abstract
中文摘要
背景：
黑色素瘤是一种高度侵袭性的皮肤恶性肿瘤，发病率超过每10万人3例。肿瘤浸润淋巴细胞（TILs）通常与更好的预后和肿瘤消退相关，反映了活跃的宿主免疫反应。然而，黑色素瘤可以逃避免疫攻击，因此炎症细胞并不总是有效的或针对肿瘤的。本研究评估了原发性皮肤黑色素瘤中不同TIL类别的肿瘤坏死因子（TNF）和干扰素-gamma（IFNgamma）表达，以确定这些浸润是作为活跃的应答者还是被动的旁观者。
方法：我们使用来自比勒陀利亚大学（2014-2020年）的存档原发性皮肤黑色素瘤组织进行了横断面研究。纳入了皮肤穿刺活检、局部切除和广泛切除标本。对福尔马林固定、石蜡包埋的切片进行了TNF和IFNgamma的免疫组织化学。三位病理学家独立地将TILs分级为阴性、非活跃（non-brisk）或活跃（brisk），并评估细胞因子表达。
结果：六十六名患者符合纳入标准。TIL分级为：阴性（39.4%）、非活跃（33.3%）和活跃（27.3%）。总体而言，31.8%的黑色素瘤为TNF阳性。TNF表达出现在16.7%的活跃TIL病例、41%的非活跃病例和15%的TIL阴性肿瘤中。IFNgamma表达显示出更清晰的梯度：活跃TILs在89%的病例中为IFNgamma阳性，非活跃在64%，TIL阴性在15%。广泛色素沉着的黑色素瘤倾向于显示低细胞因子表达，尽管数量较少，无法得出确切结论。
结论：
TNF和IFNgamma表达在原发性皮肤黑色素瘤中大体上与TIL分级相关。活跃TILs与高IFNgamma表达密切相关，非活跃TILs显示更适度的细胞因子水平，而TIL阴性肿瘤在很大程度上细胞因子含量低。这些发现提示炎症浸润之间存在功能异质性。需要更大规模、理想情况下多中心的研究，纳入更多色素沉着较重的黑色素瘤和临床结局数据，以阐明这些细胞因子模式的预后和潜在治疗意义。
查看英文原文 English abstract
Background:
Melanoma is a highly aggressive skin malignancy with an incidence exceeding 3 per 100 000. Tumor-infiltrating lymphocytes (TILs) are often linked to better prognosis and tumor regression, reflecting an active host immune response. However, melanoma can evade immune attack, so inflammatory cells are not always effective or tumor-directed. This study evaluated tumor necrosis factor (TNF) and interferon-gamma (IFNgamma) expression in primary cutaneous melanoma across different TIL categories to determine whether these infiltrates act as active responders or passive bystanders.
Methods: We performed a cross-sectional study using archival primary cutaneous melanoma tissue from the University of Pretoria (2014-2020). Skin punch biopsies, local excisions, and wide excisions were included. Immunohistochemistry for TNF and IFNgamma was performed on formalin-fixed, paraffin-embedded sections. Three pathologists independently graded TILs as negative, non-brisk, or brisk and assessed cytokine expression.
Results: Sixty-six patients met inclusion criteria. TIL grades were: negative (39.4%), non-brisk (33.3%), and brisk (27.3%). Overall, 31.8% of melanomas were TNF-positive. TNF expression occurred in 16.7% of brisk TIL cases, 41% of non-brisk cases, and 15% of TIL-negative tumors. IFNgamma expression showed a clearer gradient: brisk TILs were IFNgamma-positive in 89% of cases, non-brisk in 64%, and TIL-negative in 15%. Extensively pigmented melanomas tended to show low cytokine expression, although numbers were small and firm conclusions could not be drawn.
Conclusion
TNF and IFNgamma expression broadly correlated with TIL grade in primary cutaneous melanoma. Brisk TILs were strongly associated with high IFNgamma expression, non-brisk TILs showed more modest cytokine levels, and TIL-negative tumors were largely cytokine-poor. These findings suggest functional heterogeneity among inflammatory infiltrates. Larger, ideally multicenter studies including more heavily pigmented melanomas and clinical outcome data are needed to clarify the prognostic and potential therapeutic implications of these cytokine patterns.
利益披露 Disclosure
T. Ntuli, None..
B. Mosoane, None..
T. Marutha, None..
R. Marima, None..
Z. Dlamini, None..
M. Bida, None.