Single-cell Study Reveals How Hpv Shapes Immune Landscape In Penile Cancer

Although penile crab represents little than 1% of antheral malignancies, it carries important beingness and psychological burden, pinch a five-year endurance complaint adjacent 50%. Around half of Penile squamous compartment carcinoma (PSCC) cases are associated pinch persistent HPV infection, which triggers oncogenic translator via viral oncoproteins E6 and E7. Interestingly, HPV-positive PSCC patients thin to person amended endurance and curen responses compared to HPV-negative cases. However, nan mechanisms down this objective advantage stay poorly understood. Due to constricted diligent samples and tumor heterogeneity, erstwhile genomic studies grounded to afloat seizure nan immune microenvironment. Given these challenges, it is basal to research nan cellular ecosystem of HPV-associated PSCC utilizing single-cell approaches.

A investigation squad from nan University of Science and Technology of China has mapped nan tumor microenvironment of HPV-associated penile crab astatine single-cell resolution. The study, published (DOI: 10.1093/pcmedi/pbaf013) successful Precision Clinical Medicine successful September 2025, analyzed 52,980 azygous cells from 11 treatment-naïve PSCC patients. By comparing HPV-positive (HPV+) and HPV-negative (HPV−) tumors, nan researchers revealed profound immune differences that whitethorn explicate variations successful prognosis and therapeutic response. The single-cell atlas provides a high-resolution reference for knowing really HPV infection shapes tumor immunity and microenvironmental dynamics.

Using high-throughput single-cell RNA sequencing, nan squad profiled immune, stromal, and epithelial cells from PSCC tissues to dissect their heterogeneity. Unsupervised clustering identified 49 chopped cellular subpopulations grouped into 7 awesome compartment types, including T cells, B cells, macrophages, NK cells, endothelial cells, and cancer-associated fibroblasts (CAFs). Notably, HPV+-PSCC tumors showed an accrued abundance of mast cells but a important simplification successful proliferative macrophages compared to HPV− cases. Gene ontology study revealed that inflammatory CAFs successful HPV+-PSCC expressed higher levels of chemokines specified arsenic CXCL13, CXCL3, and CXCL12, suggesting enhanced immune recruitment. In contrast, antigen-presenting cells successful HPV− tumors upregulated CXCL5, CXCL1, and CCL13, promoting leukocyte migration and a much immunosuppressive niche. Transcriptomic profiling further revealed that CD8+ T cells successful HPV+-PSCC expressed markedly little levels of immune checkpoint molecules-including PDCD1 (PD-1), CTLA4, HAVCR2 (TIM-3), LAG3, and TIGIT-indicating reduced exhaustion and perchance greater antitumor activity. Ligand–receptor study highlighted that inhibitory signaling via TIGIT and its ligands (PVR, NECTIN2/3/4) was enriched successful HPV− tumors, reinforcing their suppressed immune environment.

"Our findings supply a broad single-cell atlas of PSCC and uncover really HPV infection remodels nan tumor ecosystem," said nan study's investigators from nan University of Science and Technology of China. "By identifying cell-type-specific immune signatures and signaling interactions, we tin amended understand why HPV-positive tumors thin to respond much favorably to therapy. These results besides stress nan value of examining viral factors erstwhile designing personalized immunotherapy strategies for uncommon cancers for illustration PSCC."

This single-cell scenery offers a important assets for early investigation connected viral-induced cancers and tumor immunology. The find that HPV-positive tumors harbor less exhausted CD8+ T cells and weaker inhibitory TIGIT–PVR signaling suggests imaginable biomarkers for prognosis and targets for immunotherapy. Therapeutic strategies aimed astatine restoring immune activation successful HPV− tumors-such arsenic TIGIT blockade aliases chemokine modulation-could heighten curen efficacy. Beyond penile cancer, this study besides provides a conceptual model for knowing really viral infections style tumor immune microenvironments crossed different crab types.

Source:

Journal reference:

Zhu, L., et al. (2025). Single-cell transcriptomic profiling reveals chopped tumor microenvironments successful HPV-associated penile squamous compartment carcinoma. Precision Clinical Medicine. doi: 10.1093/pcmedi/pbaf013. https://academic.oup.com/pcm/article/8/3/pbaf013/8249264