Tumor stromal cells (TSCs) play a crucial yet underexplored role in the tumor microenvironment (TME). This study uses single-cell sequencing and spatial transcriptomics on paired tumor specimens from 22 patients with oral squamous cell carcinoma (OSCC) enrolled in a randomized two-arm phase 2 trial, receiving neoadjuvant anti-PD-1 mono-immunotherapy or anti-PD-1 plus docetaxel-cisplatin-5-fluorouracil (TPF) immunochemotherapy. Single-cell analysis reveals increased TSCs within the TME of responders in immunochemotherapy. Notably, significant post-treatment upregulation of SELP+ high endothelial venules (HEVs) and APOD+ myofibroblastic cancer-associated fibroblasts (myCAFs), alongside a decline in STMN1+ capillary endothelial cells (cECs), is specific to the immunochemotherapy cohort. In contrast, MYF5+ muscle satellite cells (MSCs) are upregulated in non-responders to mono-immunotherapy. SELP+ HEVs and APOD+ myCAFs foster favorable immunomodulatory stromal niches for improved outcomes, while STMN1+ cECs and MYF5+ MSCs form immunosuppressive niches in tumor invasion regions, highlighting therapeutic targets. The trial was registered at ClinicalTrials.gov, and the registration number is NCT04649476.
Keywords: immunochemotherapy; neoadjuvant immunotherapy; single-cell analysis; spatial transcriptomics; stromal cell.
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