Cancers modulate processing and presentation of p53 neoantigens to evade T cell detection.

Cancers evade T cell detection by avoiding presentation of p53 neoantigens through multiple mechanisms, including mutation localization and HLA allele loss.

• Why it matters: Understanding how tumors escape immune recognition of truncal p53 neoantigens is crucial for improving immunotherapy strategies, as these mutations are present in all tumor cells and represent key targets.
• What they did: The study used comprehensive immunopeptidomics to analyze tumor samples, revealing that hotspot mutations in p53 tend to occur in regions resistant to antigen processing and that tumors often lack the relevant HLA alleles or modify antigen presentation pathways.
• The result: Tumors employ strategies such as increased ERAP1 activity and HLA allele loss to prevent display of immunogenic p53 neoantigens, highlighting mechanisms of immune escape and potential avenues for therapeutic intervention.