Abstract

Abstract Neoadjuvant chemoradiation followed by surgery is recommended for locally advanced esophageal squamous cell carcinoma (ESCC). Patients achieve pathological complete response (pCR) have better survival outcomes. Immune cells in tumor microenvironment (TME) are potential to affect chemoradiation sensitivity. Our study aimed to discover key immune-associated predictors of pCR for ESCC. The infiltrations of multiple immune cells were estimated by ImmuCellAI and cibersort based on RNA-seq data of fifty ESCC samples before treatment. The infiltrations of immune cells including Th1 cells, CD3+ T cells, CD8+ T cells, NK cells, NKT cells and DCs were evaluated by multiplex immunohistochemistry (mIHC) in 131 ESCC samples before treatment. In-vitro cell experiments were performed to discover the effects of Th1 cells on tumor cells. The analysis of RNA-seq data of ESCC revealed that the infiltration of Th1 cells was higher in pCR group. Results of mIHC demonstrated that infiltrations of Th1 cells and its relevant immune cells including CD8+ T cells, NK cells, NKT cells and DCs were positively associated with pCR. ESCC samples were divided into two subtypes based on the infiltration of these immune cells, with the high infiltration subtype was easier to achieve pCR. In-vitro cell experiments confirmed that Th1 cells were able to inhibit proliferation and improve chemoradiation sensitivity of tumor cells. Infiltrations of Th1 cells and its relevant immune cells are positively associated with pCR following neoadjuvant chemoradiation in ESCC. Th1 cells can improve the chemoradiation sensitivity of tumor cells.

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