Qinkai Zhang ^1,2 Ziyu Gao ^2* Ru Qiu ^2* Wei Qin ^3,4 Meiling Yang ⁵ Xinyue Wang ² Ciqiu Yang ^5* Jie Li ^6* Dongyang Yang ^5*

• ¹ Sun Yat-sen University, Guangzhou, China
• ² Key Laboratory of Stem Cell and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, China
• ³ Jiaying University, Meizhou, Guangdong Province, China
• ⁴ Medical College, Jiaying University, Meizhou, meizhou, China
• ⁵ Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China
• ⁶ Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong Province, China

Small cell carcinoma of the esophagus (SCCE) is a rare and aggressively progressing malignancy that presents considerable clinical challenges. Although chemotherapy can effectively manage symptoms during the early stages of SCCE, its long-term effectiveness is notably limited, with the underlying mechanisms remaining largely undefined. In this study, we employed single-cell RNA sequencing (scRNA-seq) to analyze SCCE samples from a single patient both before and after chemotherapy treatment. Our analysis revealed significant cellular plasticity and alterations in the tumor microenvironment's cellular composition. Notably, we observed an increase in tumor cell diversity coupled with reductions in T cells, B cells, and myeloid-like cells. The pre-treatment samples predominantly featured carcinoma cells in a middle transitional state, while post-treatment samples exhibited an expanded presence of cells in terminal, initial-to-terminal (IniTerm), and universally altered states.Further analysis highlighted dynamic interactions between tumor cells and immune cells, with significant changes detected in key signaling pathways, such as TIGIT-PVR and MDK-SDC4.This study elucidates the complex dynamics of cell plasticity in SCCE following chemotherapy, providing new insights and identifying potential therapeutic targets to enhance treatment efficacy.