Comprehensive Mapping of Cancer Cell Surface Peptides Reveals New Immunotherapy Targets in Melanoma and Lung Cancer

Large-scale mass spectrometry-based immunopeptidome profiling of cancer cell lines and patient samples. Databases constructed from whole-exome sequencing. De novo search algorithms used. Custom cancer germline antigen and lncRNA databases created. Key peptides validated with synthetic peptide matching and HLA binding assays.

Immunotherapy works best in high-mutation cancers. Low-mutation cancers like EGFR-driven lung cancer have been harder to target. Finding abundant displayed peptides in both cancer types, plus new sources like lncRNA, expands immunotherapy targets dramatically.

Precision immunotherapy requires knowing which peptides cancer cells display on their surface. This study dramatically expands the catalog of targetable peptides and introduces lncRNA-derived peptides as a completely new class of cancer antigens. For cancers with low mutation burden that don't respond to checkpoint inhibitors, these newly identified peptides could unlock immunotherapy approaches that were previously unavailable.

The study profiled cell lines and a limited number of patient samples. Not all identified peptides will be immunogenic (able to trigger an immune response). The lncRNA-derived peptides are novel and need functional validation in immune assays. Some findings may be specific to the HLA types studied.