biostudies-literatureRospo GAIRC under IG 2018International Accelerator Award, ACRCelerateFondazione AIRC under 5 per Mille 2018Cancer Research UKEuropean Research CouncilAIRC MFAG 2020IMI PERSIST-SEQAIRC 5x100015https://www.ebi.ac.uk/biostudies/studies/S-EPMC10797964biostudies-literatureUnknown16(1)<h4>Background</h4>Immunotherapy based on checkpoint inhibitors is highly effective in mismatch repair deficient (MMRd) colorectal cancer (CRC). These tumors carry a high number of mutations, which are predicted to translate into a wide array of neoepitopes; however, a systematic classification of the neoantigen repertoire in MMRd CRC is lacking. Mass spectrometry peptidomics has demonstrated the existence of MHC class I associated peptides (MAPs) originating from non-coding DNA regions. Based on these premises we investigated DNA genomic regions responsible for generating MMRd-induced peptides.<h4>Methods</h4>We exploited mouse CRC models in which the MMR gene Mlh1 was genetically inactivated. Isogenic cell lines CT26 Mlh1^+/+ and Mlh1^-/- were inoculated in immunocompGenome medicineNon-canonical antigens are the largest fraction of peptides presented by MHC class I in mismatch repair deficient murine colorectal cancer.PMC107979642176322737A28223contract n. 10100793722795GEACC18004TABID. 21923 projectA26825Grant-ID 24604Cancer Research UK (A26825 and A28223), FC AECC (GEACC18004TAB), and AIRC (22795)ID. 21091 program101020342grant agreement no.101020342Bartolini AGermano GBachi AMatafora VMondino ABardelli ALamba SChila RBasso VDi Nicolantonio FRospo GfalseNon-canonical antigens are the largest fraction of peptides presented by MHC class I in mismatch repair deficient murine colorectal cancer.<h4>Background</h4>Immunotherapy based on checkpoint inhibitors is highly effective in mismatch repair deficient (MMRd) colorectal cancer (CRC). These tumors carry a high number of mutations, which are predicted to translate into a wide array of neoepitopes; however, a systematic classification of the neoantigen repertoire in MMRd CRC is lacking. Mass spectrometry peptidomics has demonstrated the existence of MHC class I associated peptides (MAPs) originating from non-coding DNA regions. Based on these premises we investigated DNA genomic regions responsible for generating MMRd-induced peptides.<h4>Methods</h4>We exploited mouse CRC models in which the MMR gene Mlh1 was genetically inactivated. Isogenic cell lines CT26 Mlh1^+/+ and Mlh1^-/- were inoculated in immunocomp2024-01-01T00:00:00Z2024 Jan2026-07-15T04:47:20.356Z2025-04-04T19:22:14.289ZS-EPMC107979643824330810.1186/s13073-023-01275-3