{"id":227375,"date":"2025-12-18T01:26:17","date_gmt":"2025-12-18T07:26:17","guid":{"rendered":"https:\/\/lifeboat.com\/blog\/2025\/12\/zombie-cells-spark-inflammation-in-severe-fatty-liver-disease-mayo-clinic-researchers-find"},"modified":"2025-12-18T01:26:17","modified_gmt":"2025-12-18T07:26:17","slug":"zombie-cells-spark-inflammation-in-severe-fatty-liver-disease-mayo-clinic-researchers-find","status":"publish","type":"post","link":"https:\/\/lifeboat.com\/blog\/2025\/12\/zombie-cells-spark-inflammation-in-severe-fatty-liver-disease-mayo-clinic-researchers-find","title":{"rendered":"\u2018Zombie\u2019 cells spark inflammation in severe fatty liver disease, Mayo Clinic researchers find"},"content":{"rendered":"

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Now online! Melanoma cells escape immune surveillance by releasing MHC-antigen-loaded large EVs, known as melanosomes, that directly engage and impair CD8+ T cell receptors.<\/p>\n

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Now online! Melanoma cells and melanosomes had distinct MHC class I ligandome profiles (Figure 4 <\/a>G), but a substantial proportion of the melanosome-derived peptide repertoire overlapped with that of the parent cells (83.8%), implying derivation from the total cellular ligandome (Figure 4 <\/a>G). Pathway enrichment analysis of the immunopeptidome landscape revealed a positive correlation between pathways enriched in cells and their corresponding melanosomes, with substantial overlaps in functional categories such as class I MHC-mediated antigen processing and presentation, DNA repair, and cell cycle regulation (Figures 4 <\/a>H and 4I). Given the observed MHC class I-dependent, peptide-specific suppression of CD8+<\/sup> T cell activity by melanosomes, we hypothesized that melanosomes present immunogenic peptides. Indeed, we have identified 25 tumor-associated antigens (TAAs) in melanosome samples (Figure 4 <\/a>J) with high-confidence peptide identifications (Figure 4 <\/a>K). These TAAs are predicted to bind a variety of HLA alleles with high affinity. Strikingly, the majority of these peptides were also detected in the corresponding melanoma cell samples (Figure 4 <\/a>J). Notably, melanosomes exhibited a statistically significant enrichment in TAA presentation compared with melanoma cells, regardless of IFN\u03b3 treatment (Figure 4 <\/a>L).<\/p>\n

Finally, we used whole-exome sequencing to generate a custom proteomic database for proteogenomic analysis of neopeptides\/neoantigens. This approach identified three mutation-derived neoantigens within the human melanosome immunopeptidome, two of which were also present in the cellular MHC class I repertoire (Figures 4 <\/a>M and 4N). Importantly, we analyzed the murine B16F10 cells and secreted melanosome immunopeptidomic data, which recapitulated most of our findings in human cells (Figures S4 <\/a>A\u2013S4J). Together, these findings suggest that melanosomes, by carrying immunogenic peptides, including TAAs and neoantigens, compete with melanoma cells for CD8+<\/sup> T cell recognition, thereby contributing to their immunomodulatory effects.<\/p>\n","protected":false},"excerpt":{"rendered":"

Now online! Melanoma cells escape immune surveillance by releasing MHC-antigen-loaded large EVs, known as melanosomes, that directly engage and impair CD8+ T cell receptors. Now online! Melanoma cells and melanosomes had distinct MHC class I ligandome profiles (Figure 4 G), but a substantial proportion of the melanosome-derived peptide repertoire overlapped with that of the parent [\u2026]<\/p>\n","protected":false},"author":662,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[11],"tags":[],"class_list":["post-227375","post","type-post","status-publish","format-standard","hentry","category-biotech-medical"],"_links":{"self":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/227375","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/users\/662"}],"replies":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/comments?post=227375"}],"version-history":[{"count":0,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/227375\/revisions"}],"wp:attachment":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/media?parent=227375"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/categories?post=227375"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/tags?post=227375"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}