Experimental results demonstrate improved tumor control and survival in a melanoma model, suggesting effective modulation of the tumor microenvironment and lymph nodes.
The efficacy of cancer immunotherapy is often limited by the immunosuppressive tumor microenvironment (TME) and insufficient immune activation in tumor-draining lymph nodes (TDLN). Since the TME and TDLN form a dynamic axis crucial for tumor metastasis and resistance to immune checkpoint blockade, strategies that effectively modulate both sites are critical. Here, we present a dissolving microneedle (MN) system that generates nanomicelles (NMCs) for localized delivery of a newly identified dual-functional macrocyclic trichothecene, Roridin E (R.E). R.E induces cancer cell-autonomous secretion of IFN-β and immunogenic cancer cell death (ICD). Direct delivery of R.E to the TDLN via the MN platform reshapes the local immune landscape to suppress cancer while minimizing off-target toxicity. In a B16F10 melanoma model, MN-guided R.E. delivery significantly improved tumor control, reduced lung metastases, and extended overall survival. This approach provides a minimally invasive and effective strategy for integrating natural-product-based therapies with advanced drug delivery systems to target the TME–TDLN axis, thereby improving outcomes in metastatic cancer.
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Lim et al. (2025) studied this question.
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