ABSTRACT
Cancer-driven granulo-monocytopoiesis stimulates expansion of tumor promoting myeloid populations, mostly myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs). We identified subsets of MDSCs and TAMs based on the expression of retinoic-acid-related orphan receptor (RORC1/RORγ) in human and mouse tumor bearers. RORC1 orchestrates myelopoiesis by suppressing negative (Socs3 and Bcl3) and promoting positive (C/EBPß) regulators of granulopoiesis, as well as the key transcriptional mediators of myeloid progenitor commitment and differentiation to the monocytic/macrophage lineage (IRF8 and PU.1). RORC1 supported tumor-promoting innate immunity by protecting MDSCs from apoptosis, mediating TAM differentiation and M2 polarization, and limiting tumor infiltration by mature neutrophils. Accordingly, ablation of RORC1 in the hematopoietic compartment prevented cancer-driven myelopoiesis, resulting in inhibition of tumor growth and metastasis.
Subject(s)
Granulocytes/metabolism , Monocytes/metabolism , Myelopoiesis/genetics , Neoplasms, Experimental/genetics , Nuclear Receptor Subfamily 1, Group F, Member 3/genetics , Animals , Apoptosis/genetics , Cell Differentiation/genetics , Cell Line, Tumor , Cytokines/genetics , Cytokines/metabolism , Female , Gene Expression Regulation, Neoplastic , Granulocytes/pathology , Humans , Immunohistochemistry , Macrophages/metabolism , Macrophages/pathology , Male , Mice, 129 Strain , Mice, Inbred C57BL , Mice, Knockout , Microscopy, Confocal , Monocytes/pathology , Myeloid Cells/metabolism , Myeloid Cells/pathology , Neoplasms, Experimental/metabolism , Neoplasms, Experimental/pathology , Neutrophils/metabolism , Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Tumor Burden/geneticsABSTRACT
Peach lipid transfer protein (LTP) can cause severe allergic reactions to peach-allergic patients. It belongs to the nonspecific LTPs family, a class of proteins extremely resistant both to proteolytic digestion and to high temperatures. Food processing can either drop or increase the allergenicity, depending on the process and on the food. As far as peach-derived products (pulp, juice) are concerned, it has been previously shown how thermal treatment performed in an autoclave does not decrease LTP allergenicity. In this work, it was attempted to investigate whether sequential microwave and ultrasound processing could affect the allergenicity of peach juice. Incubation with specific anti-Pru p 3 serum showed how treating peach peel with microwave at 140 °C and with ultrasound does not eliminate Pru p 3 IgE binding properties. The application of MW/US protocol on peach pulp appeared to be insufficient for the reduction of IgE binding to Pru p 3.
