{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T02:16:44Z","timestamp":1790907404601,"version":"4.1.0"},"reference-count":62,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"37","funder":[{"name":"National Health and Medical Research Council projects of Australia","award":["APP2008698"],"award-info":[{"award-number":["APP2008698"]}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,9,11]]},"abstract":"<jats:p>The immunosuppressive tumor microenvironment (TME) remains one of the main obstacles that limit responsiveness to immunotherapy. Recently, lipid nanoparticles carrying messenger RNA (mRNA) have emerged as a promising strategy to modulate the immunosuppressive TME, with the ultimate goal of sustaining anticancer immunity of cytotoxic T lymphocytes (CTLs). However, there are challenges with mRNA-based cytokine\/chemokine therapies such as the lack of specific targeting, low therapeutic efficacy, and elevated toxicity, raising concerns about their clinical translation. Here, we have developed an antibody-coated lipid nanoparticle (Ab-LNP) delivery system that targets the protein triggering receptor expressed on myeloid cells 2 (TREM2) expressed by tumor-associated macrophages (TAMs). We demonstrate that codelivery of a Toll-like receptor agonist and CXCL9-encoding mRNA encapsulated in our Ab-LNP successfully ameliorates immunosuppression and improves tumor infiltration and activity of CTLs. Further combination with immune checkpoint inhibitors against PD-L1 and CTLA-4 promoted a CTL-favoring immunological environment and durable memory immunity. Our Ab-LNPs targeting TAMs highlight the potential of reprogramming immunosuppressive TME to enhance CTL activity for improved response to cancer immunotherapy.<\/jats:p>","DOI":"10.1126\/sciadv.aed9568","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T17:58:29Z","timestamp":1789149509000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Targeting tumor-associated macrophages using mRNA lipid nanoparticles for cytotoxic T lymphocyte\u2013mediated cancer immunotherapy"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4671-4538","authenticated-orcid":true,"given":"Rui","family":"Chen","sequence":"first","affiliation":[{"name":"School of Chemical Engineering, College of Engineering and IT, Adelaide University, Adelaide, SA, 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