Th1-involved immune infiltrates improve neoadjuvant chemoradiotherapy response of esophageal squamous cell carcinoma.
Th1-involved immune infiltrates improve neoadjuvant chemoradiotherapy response of esophageal squamous cell carcinoma.
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DOI：
10.1016/j.canlet.2022.215959
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发表时间：
2022-10
期刊：
影响因子：
9.7
通讯作者：
Jianye Yuan;Zelin Weng;Z. Tan;K. Luo;Jian Zhong;Xiuying Xie;Chunhua Qu;Xiaodan Lin;Han Yang-Ha
中科院分区：
文献类型：
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作者：
Jianye Yuan;Zelin Weng;Z. Tan;K. Luo;Jian Zhong;Xiuying Xie;Chunhua Qu;Xiaodan Lin;Han Yang-Ha
局部晚期食管鳞状细胞癌（ESCC）的治疗建议采用新辅助放化疗（NCRT）后手术治疗。达到病理完全缓解（pCR）的患者生存率更高。我们的研究旨在发现ESCC中pCR的免疫相关预测因子。在此，我们发现，从RNA测序推断的Th 1细胞浸润在pCR组中高于非pCR组。多重免疫组化（mIHC）证实，Th 1-，CD 8 +T-，NK-，NKT-和树突状细胞浸润与pCR呈正相关。Th 1细胞和CD 8 +T、NK、NKT、树突状细胞或ESCC细胞之间的空间关系是显著的pCR预测因子。根据免疫细胞浸润鉴定活动型和沙漠型，并显示不同的pCR率。体外实验证实，Th 1细胞能抑制食管鳞癌细胞的增殖，提高食管鳞癌细胞的化疗敏感性和放射敏感性。Th 1细胞上调干扰素-γ应答信号通路和抗原呈递通路，下调ESCC细胞的脂质代谢和MAPK通路。这些研究结果强调了Th 1细胞作为pCR的预测因子和ESCC的化疗敏感性和放射敏感性的调节因子的重要作用，并建议提高Th 1浸润作为改善NCRT反应的策略。
Neoadjuvant chemoradiotherapy (NCRT) followed by surgery is recommended for locally advanced esophageal squamous cell carcinoma (ESCC) treatment. Patients who achieve a pathological complete response (pCR) have better survival. Our study aimed to discover immune-associated predictors of pCR in ESCC. Herein, we found that Th1-cell infiltration inferred from RNA sequencing was higher in the pCR group than in the non-pCR group. Multiplexed immunohistochemistry (mIHC) confirmed that Th1-, CD8+T-, NK-, NKT-, and dendritic-cell infiltration was positively associated with pCR. The spatial relationships between Th1 cells and CD8+T, NK, NKT, dendritic, or ESCC cells were significant pCR predictors. The active and desert subtypes were identified based on immune cell infiltration, and showed different pCR rates. In vitro experiments confirmed that Th1 cells inhibited the proliferation and improved the chemosensitivity and radiosensitivity of ESCC cells. Th1 cells upregulated interferon-gamma response signaling and antigen presentation pathways and downregulated lipid metabolism and MAPK pathways of ESCC cells. These findings highlight the important role of Th1 cells as the predictor of pCR and the regulator of chemosensitivity and radiosensitivity of ESCC, and suggest elevating Th1-infiltration as a strategy to improve NCRT response.