Composition and Clinical Impact of the Immunologic Tumor Microenvironment in Oral Squamous Cell Carcinoma
Composition and Clinical Impact of the Immunologic Tumor Microenvironment in Oral Squamous Cell Carcinoma
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DOI：
10.4049/jimmunol.1800242
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发表时间：
2019-01-01
影响因子：
4.4
通讯作者：
Kolk, Andreas
中科院分区：
文献类型：
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作者：
Boxberg, Melanie;Leising, Lena;Kolk, Andreas
免疫疗法显示出有希望的结果，并彻底改变了口腔鳞状细胞癌（OSCC）的治疗。免疫微环境可能具有预后/预测意义。在66例人类初次治疗的OSCC中评价了形态免疫学参数（炎症浸润、基质含量和出芽活性[BA] [可能表明上皮-间质转化]）。定量上皮内/间质肿瘤浸润淋巴细胞（TIL; CD 3 +/CD 4 +/CD 8 +/CD 4 + FOXP 3 +/IL-17 A（+）），并计算比值。免疫组化法检测肿瘤细胞中HLA I类抗原的表达。进行mRNA原位杂交以检测IFN-γ。在侵入性前沿（IF）和肿瘤中心（TCe）内进行分析。HLA表达降低与低TIL密度、显著的基质含量和高BA相关; TIL中的IFN-γ与高密度TIL相关;肿瘤细胞中的IFN-γ与BA缺乏相关（p < 0.05）。参数（TCe/IF）的异质性是罕见的。TCe和IF中间质CD 4（+）FOXP 3（+）TIL的低密度被确定为总体、疾病特异性和无病生存率差的独立预后因素（p
Immunotherapy shows promising results and revolutionizes treatment of oral squamous cell carcinoma (OSCC). The immunologic microenvironment might have prognostic/predictive implications. Morphologic immunologic parameters (inflammatory infiltrate, stromal content, and budding activity [BA] [potentially indicating epithelial-mesenchymal transition]) were evaluated in 66 human primary therapy-naive OSCCs. Intraepithelial/stromal tumor-infiltrating lymphocytes (TILs; CD3+/CD4+/CD8+/CD4+ FOXP3+/IL-17A(+)) were quantified, and ratios were calculated. HLA class I in tumor cells was evaluated immunohistochemically. mRNA in situ hybridization to detect IFN-gamma was performed. Analysis was performed within invasive front (IF) and tumor center (TCe). Decreased HLA expression was associated with low TIL density, pronounced stromal content, and high BA; IFN-gamma in TILs was correlated with high-density TILs; and IFN-gamma in tumor cells was correlated with absence of BA (p < 0.05). Heterogeneity of parameters (TCe/IF) was rare. Low density of stromal CD4(+)FOXP3(+) TILs within TCe and IF was identified as an independent prognostic factor for poor overall, disease-specific, and disease-free survival (p