{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T22:52:39Z","timestamp":1793659959127,"version":"4.5.1"},"reference-count":80,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"29","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2024,7,19]]},"abstract":"<jats:p>\n                    Despite the success of immunotherapy, overcoming immunoresistance in cancer remains challenging. We identified a unique niche of tumor-associated macrophages (TAMs), coexpressing T cell immunoglobulin and mucin domain\u2013containing 3 (TIM3) and V-domain immunoglobulin suppressor of T cell activation (VISTA), that dominated human and mouse tumors resistant to most of the currently used immunotherapies. TIM3\n                    <jats:sup>+<\/jats:sup>\n                    VISTA\n                    <jats:sup>+<\/jats:sup>\n                    TAMs were sustained by IL-4\u2013enriching tumors with low (neo)antigenic and T cell\u2013depleted features. TIM3\n                    <jats:sup>+<\/jats:sup>\n                    VISTA\n                    <jats:sup>+<\/jats:sup>\n                    TAMs showed an anti-inflammatory and protumorigenic phenotype coupled with inability to sense type I interferon (IFN). This was established with cancer cells succumbing to immunogenic cell death (ICD). Dying cancer cells not only triggered autocrine type I IFNs but also exposed HMGB1\/VISTA that engaged TIM3\/VISTA on TAMs to suppress paracrine IFN-responses. Accordingly, TIM3\/VISTA blockade synergized with paclitaxel, an ICD-inducing chemotherapy, to repolarize TIM3\n                    <jats:sup>+<\/jats:sup>\n                    VISTA\n                    <jats:sup>+<\/jats:sup>\n                    TAMs to proinflammatory TAMs that killed cancer cells via tumor necrosis factor\u2013related apoptosis-inducing ligand (TRAIL) signaling. We propose targeting TIM3\n                    <jats:sup>+<\/jats:sup>\n                    VISTA\n                    <jats:sup>+<\/jats:sup>\n                    TAMs to overcome immunoresistant tumors.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adm8660","type":"journal-article","created":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T13:59:03Z","timestamp":1721397543000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":83,"title":["Targeting conserved TIM3\n                    <sup>+<\/sup>\n                    VISTA\n                    <sup>+<\/sup>\n                    tumor-associated macrophages overcomes resistance to cancer immunotherapy"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5894-6008","authenticated-orcid":true,"given":"Isaure","family":"Vanmeerbeek","sequence":"first","affiliation":[{"name":"Laboratory of Cell Stress and Immunity, Department of Cellular 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