{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T07:03:30Z","timestamp":1790492610036,"version":"4.1.0"},"reference-count":65,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T00:00:00Z","timestamp":1728518400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"ICMR-NIRRCH","award":["1568"],"award-info":[{"award-number":["1568"]}]},{"DOI":"10.13039\/501100001412","name":"Council of Scientific and Industrial Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001412","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Onco-immunotherapy via blocking checkpoint inhibitors has revolutionized the treatment-landscape of several malignancies, though not in the metastatic castration-resistant prostate cancer (PCa) owing to an immunosuppressive and poorly immunogenic \u201ccold\u201d tumor microenvironment (TME). Turning up the heat of such a cold TME via triggering innate immunity is now of increasing interest to restore immune-surveillance. Retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) are cytosolic innate-sensors that can detect exogenous RNAs and induce type-I interferons and other pro-inflammatory signaling. RIG-I activation is suggested to be a valuable addition to the treatment approaches for several cancers. However, the knowledge about RIG-I signaling in PCa remains elusive. The present study evaluated the expression of two important RLRs, RIG-I and melanoma differentiation-associated protein 5 (MDA5), along with their downstream partners, mitochondrial antiviral-signaling protein (MAVS) and ERA G-protein-like 1 (ERAL1), during PCa progression in the transgenic adenocarcinoma of mouse prostate (TRAMP) model. The early stage of PCa revealed a significant increment in the expression of RLRs but not MAVS. However, the advanced stage showed downregulated RLR signaling. Further, the therapeutic implication of 5\u02b9ppp-dsRNA, a synthetic RIG-I agonist and Bcl2 gene silencer, has been investigated in vitro and in vivo. Intra-tumoral delivery of 5\u02b9ppp-dsRNA regressed tumor growth via triggering tumor cell apoptosis, immunomodulation, and inducing phagocytic \u201ceat me\u201d signals. These findings highlight that, for the first time, RIG-I activation and Bcl-2 silencing with 5\u02b9ppp-dsRNA can serve as a potent tumor-suppressor strategy in PCa and has a significant clinical implication in transforming a \u201ccold\u201d TME into an immunogenic \u201chot\u201d TME of PCa.<\/jats:p>","DOI":"10.1093\/intimm\/dxae061","type":"journal-article","created":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T11:38:52Z","timestamp":1728560332000},"page":"109-129","source":"Crossref","is-referenced-by-count":2,"title":["Intra-tumoral delivery of 5\u02b9ppp-dsRNA induces a robust antitumor response via RIG-I activation and Bcl-2 gene downregulation in a murine model of prostate cancer"],"prefix":"10.1093","volume":"37","author":[{"given":"Kasturi","family":"Ganguly","sequence":"first","affiliation":[{"name":"Department of Innate Immunity, Indian Council of Medical Research (ICMR)-National Institute for Research in Reproductive and Child Health , Mumbai ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siddhanath M","family":"Metkari","sequence":"additional","affiliation":[{"name":"Experimental Animal Facility, Indian Council of Medical Research (ICMR)-National Institute for Research in Reproductive and Child Health , Mumbai ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barnali","family":"Biswas","sequence":"additional","affiliation":[{"name":"Department of Innate Immunity, Indian Council of Medical Research (ICMR)-National Institute for Research in Reproductive and Child Health , Mumbai ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rambhadur","family":"Subedi","sequence":"additional","affiliation":[{"name":"Department of Innate Immunity, Indian Council of Medical Research (ICMR)-National Institute for Research in Reproductive and Child Health , Mumbai ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taruna","family":"Madan","sequence":"additional","affiliation":[{"name":"Department of Innate Immunity, Indian Council of Medical Research (ICMR)-National Institute for Research in Reproductive and Child Health , Mumbai ,","place":["India"]},{"name":"Division of Development Research, Indian Council of Medical Research (ICMR) , New Delhi ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,10,10]]},"reference":[{"key":"2025010817061812300_CIT0001","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.21708","article-title":"Cancer statistics, 2022","volume":"72","author":"Siegel","year":"2022","journal-title":"CA Cancer J Clin"},{"key":"2025010817061812300_CIT0002","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.eururo.2020.09.042","article-title":"EAU-EANM-ESTRO-ESUR-SIOG guidelines on prostate cancer\u20142020 update. 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