@article{3076330,
    title = "Csf1/csf1r axis blockade limits mesothelioma and enhances efficiency of anti-pdl1 immunotherapy",
    author = "Magkouta, S.F. and Vaitsi, P.C. and Pappas, A.G. and Iliopoulou, M. and Kosti, C.N. and Psarra, K. and Kalomenidis, I.T.",
    journal = "Blood cancer journal",
    year = "2021",
    volume = "13",
    number = "11",
    publisher = "MDPI",
    doi = "10.3390/cancers13112546",
    keywords = "antineoplastic agent;  blz 945;  colony stimulating factor 1;  colony stimulating factor receptor;  colony stimulating factor receptor 1;  programmed death 1 ligand 1;  programmed death 1 ligand 1 inhibitor;  programmed death 1 receptor;  unclassified drug, animal experiment;  animal model;  animal tissue;  antineoplastic activity;  Article;  cancer growth;  cancer immunotherapy;  CD8+ T lymphocyte;  cell expansion;  cell population;  clinical effectiveness;  controlled study;  CSF1 CSF1R signaling;  disease burden;  flow cytometry;  immunofluorescence;  immunohistochemistry;  in vitro study;  lymphocyte subpopulation;  M2 tumor-associated macrophage;  mesothelioma;  mouse;  nonhuman;  protein expression;  RNA sequencing;  signal transduction;  upregulation",
    abstract = "Colony-Stimulating Factor 1 (CSF1)/Colony-Stimulating Factor Receptor 1 (CSF1R) signaling orchestrates tumor-associated macrophage (TAM) recruitment and polarization towards a pro-tumor M2 phenotype, the dominant phenotype of TAMs infiltrating mesothelioma tumors. We hypothesized that CSF1/CSF1R inhibition would halt mesothelioma growth by targeting immuno-suppressive M2 macrophages and unleashing efficient T cell responses. We also hypothesized that CSF1/CSF1R blockade would enhance the efficacy of a PDL1 inhibitor which directly activates CD8+ cells. We tested a clinically relevant CSF1R inhibitor (BLZ945) in mesothelioma treatment using syngeneic murine models. We evaluated the role of CSF1/CSF1R axis blockade in tumor-infiltrating immune subsets. We examined the effect of combined anti-CSF1R and anti-PDL1 treatment in mesothelioma progression. CSF1R inhibition impedes mesothelioma progression, abrogates infiltration of TAMs, facilitates an M1 anti-tumor phenotype and activates tumor dendritic and CD8+ T cells. CSF1R inhibition triggers a compensatory PD-1/PDL1 upregulation in tumor and immune cells. Combined CSF1R inhibitor with an anti-PDL1 agent was more effective in retarding mesothelioma growth compared to each monotherapy. In experimental mesotheliomas, CSF1R inhibition abrogates tumor progression by limiting suppressive myeloid populations and enhancing CD8+ cell activation and acts synergistically with anti-PDL1. © 2021 by the authors. Licensee MDPI, Basel, Switzerland."
}