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HSF1 excludes CD8+ T cells from breast tumors via suppression of CCL5
bioRxiv - Bioinformatics Pub Date : 2023-03-13 , DOI: 10.1101/2022.05.12.491688
Richard L. Carpenter , Haimanti Ray , John Wang , Sha Cao

Heat shock factor 1 (HSF1) is a stress-responsive transcription factor that promotes cancer cell malignancy. A novel HSF1 Activity Signature (HAS) was found to be negatively associated with antitumor immune cells in breast tumors. Knockdown of HSF1 decreased tumor size and caused an influx of several antitumor immune cells, most notably CD8+ T cells. Depletion of CD8+ T cells prevented tumors from shrinking after knockdown of HSF1, suggesting HSF1 prevents CD8+ T cell influx to avoid immune-mediated tumor killing. HSF1 was also found to suppress expression of CCL5, a chemokine for CD8+ T cells, that significantly contributed to the attraction of CD8+ T cells upon the loss of HSF1. This study demonstrates a model whereby HSF1 suppresses CCL5 leading to reduced CD8+ T cells in breast tumors that prevented immune-mediated destruction. For the first time, these studies indicate HSF1 suppresses antitumor immune activity within tumors.

中文翻译:

HSF1 通过抑制 CCL5 从乳腺肿瘤中排除 CD8+ T 细胞

热休克因子 1 (HSF1) 是一种促进癌细胞恶性肿瘤的应激反应转录因子。发现一种新的 HSF1 活性特征 (HAS) 与乳腺肿瘤中的抗肿瘤免疫细胞呈负相关。HSF1 的敲低减小了肿瘤的大小并导致了几种抗肿瘤免疫细胞的涌入,最显着的是 CD8+ T 细胞。CD8+ T 细胞的耗竭可防止肿瘤在 HSF1 敲低后缩小,这表明 HSF1 可防止 CD8+ T 细胞流入以避免免疫介导的肿瘤杀伤。还发现 HSF1 抑制 CCL5 的表达,CCL5 是 CD8+ T 细胞的趋化因子,在 HSF1 缺失后显着促进 CD8+ T 细胞的吸引。这项研究展示了一个模型,HSF1 可通过该模型抑制 CCL5,从而导致乳腺肿瘤中的 CD8+ T 细胞减少,从而防止免疫介导的破坏。
更新日期:2023-03-15
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