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However, it remains unclear how an individual dendritic cells reconciles co-incident signals from immunological opposing antigens within the tissue or tumor microenvironment, where tolerogenic self-antigen and immunogenic tumor antigen or microbes coexist. Here, using complementary\n                  <jats:italic>in vivo<\/jats:italic>\n                  fluorescent reporter systems, high-resolution imaging and endosomal profiling, we simultaneously tracked uptake, intracellular processing and cross-presentation of cutaneous self, tumor and microbial antigens in murine skin tissue, tumors and draining lymph nodes. We find that a substantial fraction of dendritic cells acquire antigen from multiple sources and that localization within endosomal compartments is dictated by antigen source. Notably, type 1 conventional dendritic cells that co-process self and tumor antigen represent a significant proportion of tumor antigen-bearing dendritic cells in the tumor and tumor draining lymph node. These dual-antigen loaded dendritic cells display a diminished capacity to prime tumor-specific CD8\n                  <jats:sup>+<\/jats:sup>\n                  T cells and a marked reduction in tumor derived peptide presented on surface MHCI, while cross-priming of self-antigen specific T cells is significantly increased. These changes occur despite equivalent or greater tumor antigen uptake relative to self-antigen and high expression of surface MHCI and costimulatory molecules. Together, these data support a model in which multiantigen processing within dendritic cells can bias peptide loading away from tumor-derived epitopes, thereby limiting tumor-specific cross-priming. Modulating the antigenic context of the tumor microenvironment or endosomal routing after antigen uptake may therefore represent a strategy to restore effective dendritic cell-mediated antitumor immunity.\n                <\/jats:p>","DOI":"10.64898\/2026.06.25.734634","type":"posted-content","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T03:51:00Z","timestamp":1782877860000},"source":"Crossref","is-referenced-by-count":0,"title":["Self-antigen disrupts cDC1 mediated antitumor responses"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4085-759X","authenticated-orcid":false,"given":"Victoria P","family":"Schuster","sequence":"first","affiliation":[{"name":"Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, Oregon, 97201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kasidy","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, Oregon, 97201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Laverde","sequence":"additional","affiliation":[{"name":"Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, Oregon, 97201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Berkowitz","sequence":"additional","affiliation":[{"name":"Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, Oregon, 97201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyssa M","family":"Granados","sequence":"additional","affiliation":[{"name":"Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, Oregon, 97201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Oshimori","sequence":"additional","affiliation":[{"name":"Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, Oregon, 97201"},{"name":"Department of Dermatology. Oregon Health & Science University, Portland, Oregon, 97201"},{"name":"Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, 97201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M","family":"Leech","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of California San Francisco, San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonin","family":"Weckel","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of California San Francisco, San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany C","family":"Scharschmidt","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of California San Francisco, San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan K","family":"Ruhland","sequence":"additional","affiliation":[{"name":"Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, Oregon, 97201"},{"name":"Department of Dermatology. Oregon Health & Science University, Portland, Oregon, 97201"},{"name":"Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, 97201"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026070303550948000_2026.06.25.734634v1.1","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/j.immuni.2024.03.014","article-title":"Control of adaptive immunity by pattern recognition receptors","volume":"57","year":"2024","journal-title":"Immunity. 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