Single-cell transcriptomics reveal the effects of chemoimmunotherapy on hypopharyngeal cancer and its tumor microenvironment

Induction chemoimmunotherapy (ICIT) has emerged as a potential treatment option for resectable hypopharyngeal cancer (HPC), while its effectiveness remains limited to a significant portion of HPC cases, and a major challenge behind lies in the lack of reliable molecular markers to identify treatment-resistant patients. In this study, we analyzed biopsy samples of HPC patients collected before and after ICIT, classifying them based on treatment response. By investigating the tumor microenvironment (TME) at the single-cell level, we demonstrated that the heterogeneity within the TME is closely linked to different treatment outcomes. Specially, a strong treatment response correlated with a subpopulation of cancer-associated fibroblasts (CAFs). Additionally, we identified that the S100A2 gene is highly expressed in tumor cells and appears to influence ICIT efficacy. Using bulk RNA sequencing, we estimated cell composition and validated these observations at the protein level. Our research provides a novel approach for identifying genes and cell populations that predict treatment responses in HPC, potentially enabling the timely identification of treatment-resistant patients. This could increase the likelihood of preserving laryngeal function and optimizing treatment strategies.