title: Pro-Tumoral Inflammatory Myeloid Cells as Emerging Therapeutic Targets.
abstract: Since the observation of Virchow, it has long been known that the tumor microenvironment constitutes the soil for the infiltration of inflammatory cells and for the release of inflammatory mediators. Under certain circumstances, inflammation remains unresolved and promotes cancer development. Here, we review some of these indisputable experimental and clinical evidences of cancer related smouldering inflammation. The most common myeloid infiltrate in solid tumors is composed of myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs). These cells promote tumor growth by several mechanisms, including their inherent immunosuppressive activity, promotion of neoangiogenesis, mediation of epithelial-mesenchymal transition and alteration of cellular metabolism. The pro-tumoral functions of TAMs and MDSCs are further enhanced by their cross-talk offering a myriad of potential anti-cancer therapeutic targets. We highlight these main pro-tumoral mechanisms of myeloid cells and give a general overview of their phenotypical and functional diversity, offering examples of possible therapeutic targets. Pharmacological targeting of inflammatory cells and molecular mediators may result in therapies improving patient condition and prognosis. Here, we review experimental and clinical findings on cancer-related inflammation with a major focus on creating an inventory of current small molecule-based therapeutic interventions targeting cancer-related inflammatory cells: TAMs and MDSCs.
authors.affiliation: Avidin Ltd., Also kikoto sor 11/D., H-6726 Szeged, Hungary. g.szebeni@avidinbiotech.com.|Synaptogenex Ltd., Őzsuta utca 20995/1, H-1037 Budapest, Hungary. g.szebeni@avidinbiotech.com.
authors.forename: Gabor J
authors.initials: GJ
authors.lastname: Szebeni
authors.affiliation: Department of Biochemistry, Biological Research Center, Hungarian Academy of Sciences, Temesvari krt. 62., H-6726 Szeged, Hungary. vizler.csaba@brc.mta.hu.
authors.forename: Csaba
authors.initials: C
authors.lastname: Vizler
authors.affiliation: Avidin Ltd., Also kikoto sor 11/D., H-6726 Szeged, Hungary. lajos@avidinbiotech.com.
authors.forename: Lajos I
authors.initials: LI
authors.lastname: Nagy
authors.affiliation: Department of Genetics, Biological Research Center, Hungarian Academy of Sciences, Temesvari krt. 62., H-6726 Szeged, Hungary. klarakitajka@gmail.com.
authors.forename: Klara
authors.initials: K
authors.lastname: Kitajka
authors.affiliation: Avidin Ltd., Also kikoto sor 11/D., H-6726 Szeged, Hungary. laszlo@avidinbiotech.com.|Department of Genetics, Biological Research Center, Hungarian Academy of Sciences, Temesvari krt. 62., H-6726 Szeged, Hungary. laszlo@avidinbiotech.com.
authors.forename: Laszlo G
authors.initials: LG
authors.lastname: Puskas
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002450:Cell Communication / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007249:Inflammation / Q000517:prevention & control; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D058990:Molecular Targeted Therapy; D000072737:Myeloid-Derived Suppressor Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D054852:Small Molecule Libraries / Q000627:therapeutic use*; D059016:Tumor Microenvironment / Q000187:drug effects* / Q000235:genetics / Q000276:immunology
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D009363:Neoplasm Proteins; D054852:Small Molecule Libraries
keywords: inflammatory tumor microenvironment; myeloid-derived suppressor cells; tumor-associated macrophages