A research team led by Professor Yong Taik Lim at the SKKU Advanced Institute of Nanotechnology (SAINT), Sungkyunkwan University (first author: Ph.D. candidate Jin-Ho Choi), announced the development of an engineered nanoplatform named t-SMC (trained immunity-mediated splenic myelopoiesis converter), which precisely targets the spleen to reverse splenic myelopoiesis toward an antitumoral immune phenotype.

In general, tumor progression severely disrupts systemic immunity. In particular, cancer cells stimulate the spleen—a critical command center that generates and regulates blood immune cells—corrupting myeloid lineage cells that should otherwise fight tumors into "protumoral immune cells" that foster tumor growth. As a result, even when primary tumors are surgically excised, this compromised immune environment frequently leads to tumor recurrence and metastasis.

To overcome these limitations, the research team engineered a bio-hybrid microbial platform (t-SMC). They employed a "peeling-off and masking-up" strategy by precisely modifying the surface of a trained immunity-inducing Mycobacterium and coating it with human serum albumin to ensure safe, stable intravenous delivery to the spleen. Furthermore, an enzyme-activatable immune booster (TLR7/8 agonist) was integrated into the platform, designed to be selectively delivered to and reprogram immune cells within the spleen.

Once delivered, the platform induces potent "trained immunity" by reprogramming the epigenetic landscape of macrophages and extramedullary hematopoietic stem cells in the spleen. In essence, it retrains suppressed and corrupted immune cells into "antitumor immune warriors" capable of launching robust attacks against cancer. Crucially, trained immunity operates through innate immune mechanisms, offering broad-spectrum protection that does not rely on specific tumor antigens. These newly trained splenic myeloid cells then travel through the bloodstream to the tumor site, transforming the immunosuppressive tumor microenvironment into a pro-inflammatory, antitumoral battleground.

In a surgical recurrence model of colon cancer, preoperative administration of t-SMC combined with standard postoperative adjuvant therapy (anti-PD-L1 immune checkpoint blockade and oxaliplatin chemotherapy) achieved complete inhibition of tumor recurrence in 50% of the treated mice and resulted in a 62.5% long-term survival rate. This demonstrates that the platform effectively turns immunologically unresponsive "cold tumors" into therapy-responsive "hot tumors," overcoming resistance to conventional checkpoint blockades.

Professor Yong Taik Lim's team stated, "This study demonstrates that a bacteria-based nanoplatform can normalize the function of the spleen—a central hub of immune regulation—and effectively block postsurgical tumor recurrence. We are currently developing subsequent cancer immunotherapies based on this same nano-immunoengineering concept. We anticipate that these technologies will evolve into preoperative neoadjuvant immunotherapies, substantially improving survival outcomes and response rates in patients with refractory cancers."

This study was supported by the Ministry of Science and ICT (MSIT), the National Research Foundation of Korea (NRF), and the Institute for Basic Science (IBS), Republic of Korea. The findings have been published online in the latest issue of Advanced Materials, a world-renowned journal in materials science and nanobiotechnology.