Spatial transcriptomic analysis of tumor microenvironment in esophageal squamous cell carcinoma with HIV infection

Human Immunodeficiency Virus (HIV) is one of the most prevalent viruses, causing significant immune depletion in affected individuals. Current treatments can control HIV and prolong patients’ lives, but new challenges have emerged. Increasing incidence of cancers occur in HIV patients. Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers observed in HIV patients. However, the spatial cellular characteristics of HIV-related ESCC have not been explored, and the differences between HIV-ESCC and typical ESCC remain unclear. We performed spatial transcriptome sequencing on HIV-ESCC samples to depict the microenvironment and employed cell communication analysis and multiplex immunofluorescence to investigate the molecular mechanism in HIV-ESCC. We found that HIV-ESCC exhibited a unique cellular composition, with fibroblasts and epithelial cells intermixed throughout the tumor tissue, lacking obvious spatial separation, while other cell types were sparse. Besides, HIV-ESCC exhibited an immune desert phenotype, characterized by a low degree of immune cell infiltration, with only a few SPP1+ macrophages showing immune resistance functions. Cell communication analysis and multiplex immunofluorescence staining revealed that tumor fibroblasts in HIV-ESCC interact with CD44+ epithelial cells via COL1A2, promoting the expression of PIK3R1 in epithelial cells. This interaction activates the PI3K-AKT signaling pathway, which contributes to the progression of HIV-ESCC. Our findings depict the spatial microenvironment of HIV-ESCC and elucidate a molecular mechanism in the progression of HIV-ESCC. This will provide us insights into the molecular basis of HIV-ESCC and potential treatment strategies.