CXCL10 elevation

Importantly, elevated CXCL10/CXCR3 signaling was recapitulated in a transgenic lung cancer mouse model. Our results show that increased CXCL10 levels during early EGFR-TKI treatment stimulate oncogenic signaling of persistent tumor cells to contribute to EGFR-TKI resistance via autocrine and paracrine pathways.

Our data suggests that patients who progressed on T cell directed therapy and went on to receive T cell mediated BiAbs, not only respond clinically, but also have hallmark expression of activation markers. T cells can be reactivated post relapse from T cell mediated therapies, indicating that T cell targeted treatments can be applied successfully in sequential order with favorable patient outcomes. We are currently performing immune profiling on more PB and bone marrow samples to further confirm these findings in a larger patient population.

Acute rise in urinary CXCL10/Cr was associated with onset of graft-associated BL. We were not able to confirm a general association of EBV viral load and urinary CXCL10. As non-invasive monitoring is implemented using biomarkers like CXCL10 in the clinic, attention will be needed to identify other uncommon, potential sources of CXCL10 elevation.

Judicious regorafenib/anti-PD1 combination therapy can inhibit tumor growth and increase survival by normalizing tumor vasculature and increasing intratumoral CXCR3+CD8 T-cell infiltration through elevated CXCL10 expression in HCC cells.