{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:23:06Z","timestamp":1787008986002,"version":"build-2736575974"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":153,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT-203990"],"award-info":[{"award-number":["PJT-203990"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Tumors downregulate NLRC5 expression to reduce MHC-I and evade CD8+ T cell\u2013mediated killing. Introducing full-length NLRC5 (N5FL) or NLRC5-CIITA chimeric protein (N5CA) can restore tumor immunogenicity. Here, we elucidated the underlying mechanisms and also evaluated the requirement of NLRC5 expression in antigen-presenting cells (APCs) of the host for tumor control.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>Nlrc5\u2212\/\u2212 and Nlrc5+\/+ mice were implanted with B16-F10 melanoma expressing N5FL or NC5A. Tumor growth, activation of lymphoid cells, their infiltration into tumors and the requirement for tumor control were assessed. The proteomes of B16-F10 cells expressing N5FL or N5CA were analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>NLRC5-expressing tumors were efficiently controlled in both Nlrc5+\/+ and Nlrc5\u2212\/\u2212 mice, characterized by infiltration of CD8+ and CD4+ cells, natural killer (NK) cells, NK T (NKT) cells and invariant NKT (iNKT) cells, increased tumor vascularization and upregulation of Ccl4 and Cxcl9 genes. Both CD8+ and NK1.1+ cells contribute to NLRC5-dependent tumor control. NLRC5 expression in the Tumor Cancer Genome Atlas\u2013skin cutaneous melanoma correlated with NK cell markers and nonclassical MHC-Ib expression. Proteomes of NLRC5-expressing tumor cells showed downmodulation of dominant tumor antigens, but displayed significant changes in the lysosome and the proteasome pathways, upregulated the protein processing in endoplasmic reticulum pathway, and downregulated the autophagy pathway, all of which could impact processing and presentation of subdominant tumor antigens.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>NLRC5 expression in APCs is dispensable for NLRC5-dependent antitumor immunity. NLRC5-dependent tumor control requires both CD8+ and NK1.1+ cells. Tumor-intrinsic NLRC5 promotes vasculature that is permissive to infiltration by antitumor immune cells. In addition to upregulating MHC-I, NLRC5 may enhance alternative antigen-processing pathways and attenuate autophagic degradation of MHC-I, thereby augmenting tumor immunogenicity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/immadv\/ltag010","type":"journal-article","created":{"date-parts":[[2026,5,31]],"date-time":"2026-05-31T11:35:38Z","timestamp":1780227338000},"source":"Crossref","is-referenced-by-count":1,"title":["NLRC5 expression within tumor cells is critical to activate adaptive and innate antitumor immune responses"],"prefix":"10.1093","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-3524-7175","authenticated-orcid":false,"given":"Akhil","family":"Shukla","sequence":"first","affiliation":[{"name":"Department of Immunology and Cell Biology, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke , Sherbrooke, QC J1H 5N4 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Cayarga","sequence":"additional","affiliation":[{"name":"Department of Immunology and Cell Biology, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke , Sherbrooke, QC J1H 5N4 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"L\u00e9vesque","sequence":"additional","affiliation":[{"name":"Department of Immunology and Cell Biology, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke , Sherbrooke, QC J1H 5N4 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois-Michel","family":"Boisvert","sequence":"additional","affiliation":[{"name":"Department of Immunology and Cell Biology, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke , Sherbrooke, QC J1H 5N4 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4563-0412","authenticated-orcid":false,"given":"Thomas 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