formed a chemokine and cytokine microarray and single‐cell RNA sequencing. This demonstrated increased levels of NK and T cell‐ derived CCL3 and CCL4, both known myeloid cell chemo‐attractants, as well as increased IFNγ from CD8 T cells. Consistent with involvement of both T and NK cells, depletion of T or NK cells alone did not entirely abrogate combination therapy, but depletion of T and NK cells together, did.To demonstrate that these findings are clinically relevant, the human CD27 mAb, varlilumab was tested in combination with anti‐ CD20 in the BCL1 model in a human CD27 transgenic background. Here, as above, the combination was superior to either single agent. Conclusions: These data demonstrate the therapeutic potential of combining a tumor‐targeting mAb with an immune stimulating mAb, through a hitherto, unexpected mechanism of action involving activation of the innate immunity. Here, anti‐CD27 indirectly increased the capacity of macrophages to perform anti‐CD20‐mediated ADCP through T and NK cell activation.Based upon these data, a U.K. multicentre phase II clinical trial examining rituximab and varlilumab in relapsed and/or refractory B‐cell lymphoma is being initiated in Spring 2017.