title: Microenvironmental interactions in classical Hodgkin lymphoma and their role in promoting tumor growth, immune escape and drug resistance.
abstract: Classical Hodgkin lymphoma (cHL) is characterized by few tumor cells surrounded by immune cells, fibroblasts, specialized mesenchymal stromal cells and endothelial cells, representing together with their products an active part of the disease. Hodgkin and Reed-Sternberg (HRS) cells can secrete cytokines/chemokines and angiogenic factors capable of recruiting and/or inducing the proliferation of the surrounding cells and can also interact with distant sites of the microenvironment by secreting exosomes. To escape from a useful anti-tumor response due to the recognition by T and NK cells, HRS cells down-regulate HLA molecules, produce immune suppressive cytokines that inhibit cytotoxic responses, and induce an immunosuppressive phenotype on T lymphocytes and Monocytes. HRS cells survive, proliferate and are protected from the cytotoxic effects of chemotherapy agents by soluble factors or by the direct contact with inflammatory and stromal cells of the tumor microenvironment (TME). A summary of the current knowledge about classical Hodgkin Lymphoma focusing on the cross-talk between tumor cells and the microenvironment leading to immune-escape, angiogenesis tumor growth/survival and drug resistance will be reviewed here.
authors.affiliation: Department of Experimental Oncology 2, CRO Aviano National Cancer Institute, Aviano, Italy. Electronic address: daldinucci@cro.it.
authors.forename: Donatella
authors.initials: D
authors.lastname: Aldinucci
authors.affiliation: Department of Experimental Oncology 2, CRO Aviano National Cancer Institute, Aviano, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Celegato
authors.affiliation: Department of Experimental Oncology 2, CRO Aviano National Cancer Institute, Aviano, Italy.
authors.forename: Naike
authors.initials: N
authors.lastname: Casagrande
mesh_terms: D042501:Angiogenic Proteins / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002450:Cell Communication / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009389:Neovascularization, Pathologic; D015398:Signal Transduction / Q000187:drug effects; D019139:Tumor Escape; D059016:Tumor Microenvironment
chemical_list: D042501:Angiogenic Proteins; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D016207:Cytokines
keywords: Angiogenesis; Drug-resistance; Hodgkin lymphoma; Immune-escape; Tumor microenvironment