Improving Efficacy Of Pd-1 Blockade In Unresponsive Lymphoma Tumors With In Situ Vaccination Through Induction Of A Highly Efficient Cross-Presenting Dendritic Cell Subset.

76Background: Low-grade non-Hodgkin’s B-cell lymphomas are generally incurable; preliminary results with anti-PD-1 therapy have yielded low response rates. Tumoral DC infiltration correlates with efficacy of checkpoint blockade and tumor-targeted vaccines represent promising, novel treatment strategies to induce anti-tumor T cells. Methods: A20 lymphoma-bearing mice were treated with a PD-1 blocking antibody with an in situ vaccine (ISV) consisting of intratumoral injections of FMS-like tyrosine kinase-3 ligand (Flt3L), local irradiation (XRT) of the tumor and intratumoral injections of the TLR3 agonist poly-ICLC (pIC). Results: Untreated lymphoma tumors contained very low numbers of DC and treatment with anti-PD1 alone did not induce tumor regression or increase survival. Flt3L treatment resulted in a dramatic increase of IRF8+TLR3+ DC at the tumor site, the draining lymph node and the spleen. XRT of A20 cells induced activation of Flt3L-treated splenic DC in vitro and local XRT of the tumor in vivo indu...