Inhibition of Vps34 reprograms cold into hot inflamed tumors and improves anti–PD-1/PD-L1 immunotherapy
Muhammad Zaeem Noman, Santiago Parpal, Kris Van Moer, Malina Xiao, Yasmin Yu, Tsolère Arakelian, Jenny Viklund, Angelo De Milito, Meriem Hasmim, Martin Andersson, Ravi K. Amaravadi, Jessica Martinsson, Guy Berchem, Bassam Janji
Abstract
T effector cells in melanoma and CRC tumors. Such infiltration resulted in the establishment of a T cell-inflamed tumor microenvironment, characterized by the up-regulation of pro-inflammatory chemokines and cytokines, CCL5, CXCL10, and IFNγ. Vps34i treatment induced STAT1 and IRF7, involved in the up-regulation of CCL5 and CXCL10. Combining Vps34i improved the therapeutic benefit of anti-PD-L1/PD-1 in melanoma and CRC and prolonged mice survival. Our study revealed that targeting Vps34 turns cold into hot inflamed tumors, thus enhancing the efficacy of anti-PD-L1/PD-1 blockade.