Abstract 15P
Background
There is a lack of effective predictor for pCR of neoadjuvant immunotherapy in esophageal squamous cell carcinoma (ESCC) patients. High-throughput single-cell RNA sequencing (scRNAseq) can define the tumor microenvironment (TME), tumor heterogeneity and immune microenvironment. In this study, we sought to explore the immune pathways related to treatment response of immunotherapy by scRNAseq.
Methods
This was a single-arm phase II clinical trial, planned to enroll 20 locally advanced ESCC patients (cT2-4N0-1M0). Patients received neoadjuvant chemotherapy (paclitaxel-albumin + carboplatin) combined with tislelizumab and followed by minimaly invasive esophagectomy (MIE). We conducted a scRNAseq using fresh tumor tissues taken by endoscopy before neoadjuvant therapy. Histological outcome was divided into pCR (no residual tumor cells in tumor and lymph nodes), MPR (<10% residual tumor – excludes pCR) and non-MPR (>10% residual tumor).
Results
17 patients were enrolled since March,2022. 7 of 17 patients finished neoadjuvant therapy and MIE surgery. Among these 7 patients, 3 achieved pCR, 1 got MPR, and 3 were non-MPR, with a total of 42808 single cells sequenced. Compared to non-MPR, there were significantly increase in T lymphocytes (CD8+, T helper cell, Regulatory T cell) and mature dendritic cells, and significantly decrease in B cells and neutrophils in pCR patients. Morever, pCR patients showed greatly increase on the expression of PD-L1(CD274) in mature dendritic cells.
Conclusions
This study identified novel immunological predictor in baseline tissue for ESCC neoadjuvant immunotherapy. The enrichment of T lymphocytes (CD8+, T helper cell, Regulatory T cell) and mature dendritic cells together with the increase expression of PD-L1(CD274) in mature dendritic cells suggest a promising role of predicting completed pathological response (pCR) induced by neoadjuvant chemotherapy and immunotherapy in locally advanced ESCC patients.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.