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Research Highlight: Basal Cell Carcinoma’s Low Immunogenicity Linked to Antigen Presentation Suppression from Its Cellular Origin
- Basal cell carcinoma (BCC), despite being highly mutated, exhibits low immunogenicity, making it resistant to immune-based therapies.
- A study by Dr. Shawn Demehri at Massachusetts General Hospital reveals the epigenomic basis of BCC's immune evasion.
- BCC cells suppress HLA-I expression, cloaking themselves from immune detection, linked to their cell of origin and stemness programs.
- Compared to SCCs, BCCs have an immune-excluded microenvironment with minimal T cell infiltration and downregulated antigen presentation machinery.
- The transcription factor Foxc1 represses genes involved in antigen presentation in BCC cells, contributing to immune evasion.
- Entinostat, in combination with imiquimod, reverses APM suppression, enhancing antigen presentation and immune cell infiltration.
- Targeting epigenetic regulators like Foxc1 can sensitize resistant tumors like BCC to immune-based therapies, broadening treatment options.
- These findings challenge the importance of tumor mutational burden in predicting immunotherapy success.
- By understanding tumor cell origin and epigenetic regulation, new avenues for cancer immunotherapy can emerge.
- This research offers hope for improving outcomes for patients with BCC through novel combination therapies targeting stemness and immune evasion mechanisms.
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