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Since differences in matrix components, cell adhesion biology, and innate immune signaling correlated with myeloid cell response and phenotype, we hypothesized that RT combined with CD40 agonist antibody would sensitize unresponsive tumors. The combination therapy resulted improved innate and adaptive immune response. Importantly, CD40 treatment increased tumor response to RT and protected against metastatic spread in a metastatic model. CONCLUSIONS These data combined with transcriptomics from human patients supports RT and myeloid cel