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To address this clinical challenge, we developed an engineered Trojan Mycobacterium as a trained immunity (TI)\u2010mediated splenic myelopoiesis converter (t\u2010SMC). This design provides an intravenously injectable anisotropic TI inducer with an aspect ratio of 3.6 for preferential spleen targeting and cellular uptake via a Mycobacterium \u201cpeeling\u2010off and masking\u2010up\u201d strategy with human serum albumin incorporating an enzyme\u2011activatable Toll\u2011like receptor 7\/8 agonist that boosts TI activation. t\u2010SMC induces antitumoral myelopoiesis with metabolic and epigenetic reprogramming in splenic macrophages. This shift toward antitumoral myelopoiesis markedly enriches the tumor microenvironment with inflammatory myeloid effectors in an E.G7\u2010OVA model, and the adoptive transfer of splenic myeloid cells confirmed the TI\u2010driven antitumor effect. Furthermore, comparative analysis revealed that the bacterial scaffold (alb\u2010Mycobac) initiates myeloid reprogramming, but only the integrated TLR7\/8 agonist (t\u2010SMC) crosses the therapeutic threshold for tumor regression. In the MC38 surgical recurrence model, preoperative t\u2010SMC combined with standard adjuvant \u03b1PD\u2010L1 plus oxaliplatin achieved complete inhibition of recurrence in 50% of treated mice (3 of 6) with 62.5% long\u2010term survival, establishing TI priming as a translation\u2010ready preoperative adjuvant that converts immune\u2010checkpoint non\u2010responders into responders.<\/jats:p>","DOI":"10.1002\/adma.74513","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T13:59:57Z","timestamp":1785938397000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Anisotropic Masked Mycobacterium Potentiates Amplified Antitumor Trained Immunity via Spleen Targeting and Myelopoiesis 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