Multi-omics exploration of CAV1 tumor epithelial subcelltype in oral squamous cell carcinoma and its impact on the immune microenvironment.

BACKGROUND

Oral squamous cell carcinoma originating from the gingiva and buccal mucosa (OSCC-GB) is closely associated with complex molecular mechanisms and immune evasion phenomena within the tumor microenvironment. This study aims to reveal the characteristics of tumor epithelial cell subcelltypes and their roles in tumor progression.

METHODS

We organized and analyzed single-cell RNA sequencing (scRNA-seq) data from Oral squamous cell carcinoma (OSCC), categorizing tumor epithelial cells into six subcelltypes. Utilizing spatial transcriptomics, we investigated the spatial distribution of these subcelltypes. The focus was on the high malignancy tumor epithelial subcelltype, aiming to identify specific transcription factors and analyze their effects on cell status and function. Furthermore, we examined the interactions between the high malignancy tumor epithelial subcelltype and immune cells within the tumor immune microenvironment, along with the underlying mechanisms.

RESULTS

Our findings indicate that the CAV1 epithelial subcelltype (CAV1EIP) exhibits the highest copy number variation scores, significantly correlating with poor patient prognosis. Analysis of specific transcription factors reveals that high expression of LHX1 and ATF1 is associated with malignant features, while IGF2BP1, a target gene of these transcription factors, shows a negative correlation with immune regulatory pathways. Further investigations demonstrate that CAV1EIP interacts with T cells through the NECTIN1-CD96 signaling network, potentially leading to immune evasion and tumor progression.

CONCLUSION

This study elucidates the critical role of the CAV1EIP in the development of OSCC and its interplay with the immune microenvironment. These findings provide new insights into how tumor cells evade immune surveillance and guide future immunotherapeutic strategies.