Inflammatory factors in the microenvironment with implication in the development of hematopoietic malignancies
| Effector molecules/cellular source . | Target cells . | Cellular changes . | Functional effect . | Reference . | Year . |
|---|---|---|---|---|---|
| Arg1 | |||||
| MDSCs, MSCs | Arg depletion, TCR ↓ | TC anergy | 90 | 2009 | |
| IDO1/2 | CD8+ TCs, NKCs, NK-TCs | Trp depletion, mTOR activation | Proliferation arrest | 91 | 2012 |
| Production of kynurenine derivatives, AhR activation | Treg differentiation | 92 | 2010 | ||
| iNOS | TCs | NO production | Treg differentiation | 93 | 2006 |
| IL-10 | |||||
| MDSCs, MSCs | Macrophages, DCs | Inhibition of APCs | 94 | 2015 | |
| TGF-β | |||||
| MDSCs, megakaryocytes | CD4+ TCs | Foxp3 ↑ | Treg differentiation | 95 | 2010 |
| Schwann cells | IL-12Rβ2 ↓ | Inhibition of Th1 differentiation | |||
| GATA-3 ↓ STAT6↓ | Inhibition of Th2 differentiation | ||||
| S100A8 | |||||
| Neutrophils, monocytes | MDSCs | CD33 activation | MDSC expansion | 96 | 2008 |
| Macrophages, MDSCs | Sustained inflammatory response | 75 | 2019 | ||
| HSPCs | TLR4 activation, p53 activation, NFκB activation, ROS ↑, DNA damage response | HSPC loss and leukemic evolution | 68 | 2016 | |
| Erythroid precursors | TLR4 activation, p53 activation | Erythroid differentiation defect | 66 | 2016 | |
| MSCs | Loss of hematopoiesis support | 70 | 2019 | ||
| IFN-γ | |||||
| Th1 cells, macrophages | HSCs | STAT1 activation, SOCS1/SOCS3 activation | Responsiveness to growth factors ↓ | 23 | 2014 |
| CD8+ T cells | Fas↑, caspase activity ↑ | Self-renewal, repopulation capacity ↓ | |||
| Erythroid precursors | EpoR↓ PU.1↑ | Myeloid priming of MPPs, erythroid differentiation ↓ | 28 | 2007 | |
| MSCs | IL-6 induction | 97 | 2014 | ||
| TNF-α | |||||
| Adipocytes, macrophages | MPPs | Caspase-1 induction → GATA-1 cleavage | 30 | 2005 | |
| IL-6 | |||||
| MSCs, macrophages | Hepatocytes | Hepcidin induction → iron depletion | Hb biosynthesis ↓ | 27 | 2005 |
| EC | G-CSF ↑ | 40 | 1986 | ||
| G-CSF | |||||
| EC | MSCs | Stimulation of myelopoiesis | 39 | 2014 | |
| Inhibition of lymphopoiesis | |||||
| CXCL12 ↓ mobilization | 34 | 2012 | |||
| IL-1α/β | |||||
| DCs, monocytes | Sympathetic nerve fibers | Sympathetic neuropathy | 81 | 2014 | |
| Macrophages | 80 | 2014 | |||
| Senescent cells | SASP induction | 46 | 2009 | ||
| 45 | 2010 | ||||
| HSCs | TLR4 signaling, p38-MAPK activation | 98 | 2017 |
| Effector molecules/cellular source . | Target cells . | Cellular changes . | Functional effect . | Reference . | Year . |
|---|---|---|---|---|---|
| Arg1 | |||||
| MDSCs, MSCs | Arg depletion, TCR ↓ | TC anergy | 90 | 2009 | |
| IDO1/2 | CD8+ TCs, NKCs, NK-TCs | Trp depletion, mTOR activation | Proliferation arrest | 91 | 2012 |
| Production of kynurenine derivatives, AhR activation | Treg differentiation | 92 | 2010 | ||
| iNOS | TCs | NO production | Treg differentiation | 93 | 2006 |
| IL-10 | |||||
| MDSCs, MSCs | Macrophages, DCs | Inhibition of APCs | 94 | 2015 | |
| TGF-β | |||||
| MDSCs, megakaryocytes | CD4+ TCs | Foxp3 ↑ | Treg differentiation | 95 | 2010 |
| Schwann cells | IL-12Rβ2 ↓ | Inhibition of Th1 differentiation | |||
| GATA-3 ↓ STAT6↓ | Inhibition of Th2 differentiation | ||||
| S100A8 | |||||
| Neutrophils, monocytes | MDSCs | CD33 activation | MDSC expansion | 96 | 2008 |
| Macrophages, MDSCs | Sustained inflammatory response | 75 | 2019 | ||
| HSPCs | TLR4 activation, p53 activation, NFκB activation, ROS ↑, DNA damage response | HSPC loss and leukemic evolution | 68 | 2016 | |
| Erythroid precursors | TLR4 activation, p53 activation | Erythroid differentiation defect | 66 | 2016 | |
| MSCs | Loss of hematopoiesis support | 70 | 2019 | ||
| IFN-γ | |||||
| Th1 cells, macrophages | HSCs | STAT1 activation, SOCS1/SOCS3 activation | Responsiveness to growth factors ↓ | 23 | 2014 |
| CD8+ T cells | Fas↑, caspase activity ↑ | Self-renewal, repopulation capacity ↓ | |||
| Erythroid precursors | EpoR↓ PU.1↑ | Myeloid priming of MPPs, erythroid differentiation ↓ | 28 | 2007 | |
| MSCs | IL-6 induction | 97 | 2014 | ||
| TNF-α | |||||
| Adipocytes, macrophages | MPPs | Caspase-1 induction → GATA-1 cleavage | 30 | 2005 | |
| IL-6 | |||||
| MSCs, macrophages | Hepatocytes | Hepcidin induction → iron depletion | Hb biosynthesis ↓ | 27 | 2005 |
| EC | G-CSF ↑ | 40 | 1986 | ||
| G-CSF | |||||
| EC | MSCs | Stimulation of myelopoiesis | 39 | 2014 | |
| Inhibition of lymphopoiesis | |||||
| CXCL12 ↓ mobilization | 34 | 2012 | |||
| IL-1α/β | |||||
| DCs, monocytes | Sympathetic nerve fibers | Sympathetic neuropathy | 81 | 2014 | |
| Macrophages | 80 | 2014 | |||
| Senescent cells | SASP induction | 46 | 2009 | ||
| 45 | 2010 | ||||
| HSCs | TLR4 signaling, p38-MAPK activation | 98 | 2017 |
AhR, aryl hydrocarbon receptor; APC, antigen-presenting cell; Arg1, arginase 1; DC, dendritic cell; Hb, hemoglobin; IDO, indoleamine 2, 3-dioxygenase; iNOS, inducible nitric oxide synthase; MDSC, myeloid-derived suppressor cell; NKC, natural killer cell; NKT, natural killer T cell; NO, nitric oxide; ROS, reactive oxygen species; TC, T cell; TCR, T-cell receptor; Th, T helper; Treg, regulatory T cell; Trp, tryptophan.