γδ T 细胞调节小细胞肺癌中的抗肿瘤免疫
γδ T cells modulate anti-tumor immunity in small cell lung cancer.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Tumor-Infiltrating T Cells in Skin Basal Cell Carcinomas and Squamous Cell Carcinomas: Global Th1 Preponderance with Th17 Enrichment-A Cross-Sectional Study.
Tumor-Infiltrating T Cells in Skin Basal Cell Carcinomas and Squamous Cell Carcinomas: Global Th1 Preponderance with Th17 Enrichment-A Cross-Sectional Study.
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基底细胞癌(BCC)和鳞状细胞癌(SCC)是高发病率的非黑色素瘤皮肤癌(NMSC)。免疫靶向治疗在晚期NMSC中的成功使我们预期NMSC中存在大量具有潜在抗肿瘤活性的TIL(肿瘤浸润淋巴细胞)。
本研究的主要目的是表征浸润NMSC的T细胞。采用流式细胞术和免疫组织化学分别评估BCC(n = 118)、SCC(n = 33)和正常皮肤(NS,n = 30)中T细胞亚群的比例和密度。比较了NMSC与NS样本之间的CD8+ T细胞、CD4+ T细胞亚群(即Th1、Th2、Th17、Th9和调节性T细胞(Treg))、CD8+和CD4+记忆T细胞以及γδ T细胞。
值得注意的是,BCC和SCC均表现出显著更高的Th1/Th2比值(约四倍)以及Th17细胞的富集。NMSC还显示出产生IFN-γ的CD8+ T细胞的显著富集以及γδ T细胞的减少。使用免疫组织化学,NMSC表现出比NS更密集的T细胞浸润(CD4+、CD8+和Treg)。
总体而言,这些数据支持BCC和SCC中以Th1为主的反应,为NMSC的免疫治疗提供了支持。Th17介导的炎症可能在NMSC的进展中发挥作用,因此成为NMSC的潜在治疗靶点。
Basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) are high-incidence, non-melanoma skin cancers (NMSCs). The success of immune-targeted therapies in advanced NMSCs led us to anticipate that NMSCs harbored significant populations of tumor-infiltrating lymphocytes with potential anti-tumor activity. The main aim of this study was to characterize T cells infiltrating NMSCs. Flow cytometry and immunohistochemistry were used to assess, respectively, the proportions and densities of T cell subpopulations in BCCs (n = 118), SCCs (n = 33), and normal skin (NS, n = 30).
CD8+ T cells, CD4+ T cell subsets, namely, Th1, Th2, Th17, Th9, and regulatory T cells (Tregs), CD8+ and CD4+ memory T cells, and γδ T cells were compared between NMSCs and NS samples. Remarkably, both BCCs and SCCs featured a significantly higher Th1/Th2 ratio (~four-fold) and an enrichment for Th17 cells. NMSCs also showed a significant enrichment for IFN-γ-producing CD8+T cells, and a depletion of γδ T cells. Using immunohistochemistry, NMSCs featured denser T cell infiltrates (CD4+, CD8+, and Tregs) than NS.
Overall, these data favor a Th1-predominant response in BCCs and SCCs, providing support for immune-based treatments in NMSCs. Th17-mediated inflammation may play a role in the progression of NMSCs and thus become a potential therapeutic target in NMSCs.
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