Background:Penile squamous cell carcinoma(PSCC)is a rare yet potentially lethal malignancy,often resulting in devastating disfigurement,with a 5-year survival rate of only -50%.Human papillomavirus(HPV)infection is im...Background:Penile squamous cell carcinoma(PSCC)is a rare yet potentially lethal malignancy,often resulting in devastating disfigurement,with a 5-year survival rate of only -50%.Human papillomavirus(HPV)infection is implicated in approximately half of PSCCcases and is associated with improved clinical outcomes;however,the underlying mechanisms remain poorly understood.Methods:To elucidate HPV-associated differences in the tumor microenvironment,we performed single-cell RNA sequencing ontumors from 11 treatment-naive PSCC patients,analyzing a total of 52980 single cells.Unsupervised clustering identified 49 distinctcellular clusters across immune and stromal compartments.Results:HPV-positive tumors exhibited an increased abundance of mast cells and a reduction in the proliferative macrophages subpopulation compared to HPV-negative tumors.Notably,CD8^(+)T cells in HPV-positive PSCC expressed lower levels of immune checkpoint molecules,suggesting a less exhausted immune state.Conversely,TIGIT and its ligands were significantly enriched in HPV-negative tumors,potentially fostering an immunosuppressive niche.Conclusion:Collectively,our study delineates the single-cell landscape of PSCC and highlights distinct tumor microenvironmentremodeling associated with HPV status,suggesting that the reduced immunosuppression in HPV-positive tumors may underlie theirmore favorable prognosis.展开更多
基金supported by the Key Research and DevelopmentProgram of Anhui Province(grant No.202204295107020003 toT.T.)the Distinguished Young Scholars Fund of Anhui Province(grant No.2022AH020078 to T.T.)+1 种基金Major Joint Project of NewMedicine of USTC(grant No.YD9110002018 to T.T.)Anhui Provincial Cancer Hospital Project(grant No.QLGC 2024003to T.T.).
文摘Background:Penile squamous cell carcinoma(PSCC)is a rare yet potentially lethal malignancy,often resulting in devastating disfigurement,with a 5-year survival rate of only -50%.Human papillomavirus(HPV)infection is implicated in approximately half of PSCCcases and is associated with improved clinical outcomes;however,the underlying mechanisms remain poorly understood.Methods:To elucidate HPV-associated differences in the tumor microenvironment,we performed single-cell RNA sequencing ontumors from 11 treatment-naive PSCC patients,analyzing a total of 52980 single cells.Unsupervised clustering identified 49 distinctcellular clusters across immune and stromal compartments.Results:HPV-positive tumors exhibited an increased abundance of mast cells and a reduction in the proliferative macrophages subpopulation compared to HPV-negative tumors.Notably,CD8^(+)T cells in HPV-positive PSCC expressed lower levels of immune checkpoint molecules,suggesting a less exhausted immune state.Conversely,TIGIT and its ligands were significantly enriched in HPV-negative tumors,potentially fostering an immunosuppressive niche.Conclusion:Collectively,our study delineates the single-cell landscape of PSCC and highlights distinct tumor microenvironmentremodeling associated with HPV status,suggesting that the reduced immunosuppression in HPV-positive tumors may underlie theirmore favorable prognosis.
