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

Cancers evade T cell detection by restricting presentation of p53 neoantigens, with 70% of hotspot mutations avoiding display in tumors.

• Why it matters: Understanding how tumors escape immune recognition of early, truncal mutations like p53 is crucial for developing effective immunotherapies, as these mutations are present in all tumor cells.
• What they did: The study used comprehensive immunopeptidomics to analyze neoantigen processing, revealing that tumors resist presentation by mutating or downregulating HLA alleles and increasing ERAP1 activity, affecting neoantigen display.
• The result: Findings highlight tumor strategies to limit neoantigen visibility, informing approaches to overcome immune escape and improve targeted immunotherapies against truncal mutations like p53.