AUTHOR=Benguigui Madeleine , Vorontsova Avital , Timaner Michael , Levin Sapir , Haj-Shomaly Jozafina , Deo Abhilash , Menachem Rotem , Manobla Bar , Cooper Tim J. , Raviv Ziv , Shaked Yuval TITLE=Bv8 Blockade Sensitizes Anti-PD1 Therapy Resistant Tumors JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.903591 DOI=10.3389/fimmu.2022.903591 ISSN=1664-3224 ABSTRACT=
Myeloid-derived suppressor cells (MDSCs) are known to promote tumor growth in part by their immunosuppressive activities and their angiogenesis support. It has been shown that Bv8 blockade inhibits the recruitment of MDSCs to tumors, thereby delaying tumor relapse associated with resistance to antiangiogenic therapy. However, the impact of Bv8 blockade on tumors resistant to the new immunotherapy drugs based on the blockade of immune checkpoints has not been investigated. Here, we demonstrate that granulocytic-MDSCs (G-MDSCs) are enriched in anti-PD1 resistant tumors. Importantly, resistance to anti-PD1 monotherapy is reversed upon switching to a combined regimen comprised of anti-Bv8 and anti-PD1 antibodies. This effect is associated with a decreased level of G-MDSCs and enrichment of active cytotoxic T cells in tumors. The blockade of anti-Bv8 has shown efficacy also in hyperprogressive phenotype of anti-PD1-treated tumors.