Idel Christian, Ribbat-Idel Julika, Klapper Luise, Krupar Rosemarie, Bruchhage Karl-Ludwig, Dreyer Eva, Rades Dirk, Polasky Christina, Offermann Anne, Kirfel Jutta, Perner Sven, Wollenberg Barbara
Department of Otorhinolaryngology, University of Luebeck, Luebeck, Germany.
Institute of Pathology, University of Luebeck and University Hospital Schleswig-Holstein, Luebeck, Germany.
Front Oncol. 2021 Oct 28;11:712788. doi: 10.3389/fonc.2021.712788. eCollection 2021.
Head and neck squamous cell carcinomas (HNSCCs) have a very moderate response rate to immune checkpoint inhibitor (ICI) treatment compared to other cancer types. Lacking predictive markers for treatment response, we analyzed the immune status of HNSCC and assessed the spatial distribution of immune cells.
assessing hematoxylin-eosin (H&E) stains, we divided HNSCCs by the immune cell distribution in hot, cold, and excluded tumors. For each group, each with 10 tumors, we performed serial immunohistochemical (IHC) staining of the immune cell markers, checkpoint molecules, and immune regulators.
The spatial distributions were different for each immune cell type, allocating regulatory T cells (Tregs) and CD11b cells predominantly in the stroma. CD4 and CD8 cells were present either in the tumor stroma or between cancer cells. Interestingly, the expressions of PD-1 (programmed cell death 1 receptor) and PD-L1 (programmed death-ligand 1) were higher in hot tumors in comparison to cold and excluded tumors. The expression of pSMAD [indicating active transforming growth factor beta (TGF-β)] was higher in excluded tumors.
Different immune cell distribution patterns within tumors might be crucial for ICI treatment response since hot tumors have the highest expressions of PD-1 and PD-L1. TGF-β might be a key regulator for immune cell distribution and a promising therapeutic target that determines the formation of hot or excluded immune patterns.
与其他癌症类型相比，头颈部鳞状细胞癌（HNSCC）对免疫检查点抑制剂（ICI）治疗的反应率非常适中。由于缺乏治疗反应的预测标志物，我们分析了HNSCC的免疫状态并评估了免疫细胞的空间分布。
通过评估苏木精-伊红（H&E）染色，我们根据免疫细胞在热肿瘤、冷肿瘤和排除肿瘤中的分布对头颈部鳞状细胞癌进行了分类。对于每组，每组有10个肿瘤，我们对免疫细胞标志物、检查点分子和免疫调节因子进行了系列免疫组织化学（IHC）染色。
每种免疫细胞类型的空间分布都不同，调节性T细胞（Tregs）和CD11b细胞主要分布在基质中。CD4和CD8细胞存在于肿瘤基质中或癌细胞之间。有趣的是，与冷肿瘤和排除肿瘤相比，热肿瘤中程序性死亡受体1（PD-1）和程序性死亡配体1（PD-L1）的表达更高。排除肿瘤中磷酸化SMAD（表明活性转化生长因子β（TGF-β））的表达更高。
肿瘤内不同的免疫细胞分布模式可能对ICI治疗反应至关重要，因为热肿瘤中PD-1和PD-L1的表达最高。TGF-β可能是免疫细胞分布的关键调节因子，也是决定热免疫模式或排除免疫模式形成的有前景的治疗靶点。
