The Development and Homing of Myeloid-Derived Suppressor Cells: From a Two-Stage Model to a Multistep Narrative
Myeloid-derived suppressor cells (MDSC) represent a heterogeneous population of immature myeloid cells. Under normal conditions, they differentiate into macrophages, dendritic cells, and granulocytes. Under pathological conditions, such as chronic inflammation, or cancer, they tend to maintain their...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2020.557586/full |
| _version_ | 1818450026180902912 |
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| author | Nathan Karin |
| author_facet | Nathan Karin |
| author_sort | Nathan Karin |
| collection | DOAJ |
| description | Myeloid-derived suppressor cells (MDSC) represent a heterogeneous population of immature myeloid cells. Under normal conditions, they differentiate into macrophages, dendritic cells, and granulocytes. Under pathological conditions, such as chronic inflammation, or cancer, they tend to maintain their immature state as immature myeloid cells that, within the tumor microenvironment, become suppressor cells and assist tumor escape from immune eradication. MDSC are comprised of two major subsets: monocytic MDSC (M-MDSC) and polymorphonuclear MDSC (PMN-MDSC). Monocytic myeloid cells give rise to monocytic cells, whereas PMN-MDSC share similarities with neutrophils. Based on their biological activities, a two-stage model that includes the mobilization of the periphery as myeloid cells and their activation within the tumor microenvironment converting them into suppressor cells was previously suggested by D. Gabrilovich. From the migratory viewpoint, we are suggesting a more complex setup. It starts with crosstalk between the tumor site and the hematopoietic stem and progenitor cells (HSPCs) at the bone marrow (BM) and secondary lymphatic organs, resulting in rapid myelopoiesis followed by mobilization to the blood. Although myelopoiesis is coordinated by several cytokines and transcription factors, mobilization is selectively directed by chemokine receptors and may differ between M-MDSC and PMN-MDSC. These myeloid cells may then undergo further expansion at these secondary lymphatic organs and then home to the tumor site. Finally, selective homing of T cell subsets has been associated with retention at the target organs directed by adhesion molecules or chemokine receptors. The possible relevance to myeloid cells is still speculative but is discussed. |
| first_indexed | 2024-12-14T20:44:45Z |
| format | Article |
| id | doaj.art-110611bbba914aff8879c579753c7ddf |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-14T20:44:45Z |
| publishDate | 2020-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-110611bbba914aff8879c579753c7ddf2022-12-21T22:48:07ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-10-011110.3389/fimmu.2020.557586557586The Development and Homing of Myeloid-Derived Suppressor Cells: From a Two-Stage Model to a Multistep NarrativeNathan KarinMyeloid-derived suppressor cells (MDSC) represent a heterogeneous population of immature myeloid cells. Under normal conditions, they differentiate into macrophages, dendritic cells, and granulocytes. Under pathological conditions, such as chronic inflammation, or cancer, they tend to maintain their immature state as immature myeloid cells that, within the tumor microenvironment, become suppressor cells and assist tumor escape from immune eradication. MDSC are comprised of two major subsets: monocytic MDSC (M-MDSC) and polymorphonuclear MDSC (PMN-MDSC). Monocytic myeloid cells give rise to monocytic cells, whereas PMN-MDSC share similarities with neutrophils. Based on their biological activities, a two-stage model that includes the mobilization of the periphery as myeloid cells and their activation within the tumor microenvironment converting them into suppressor cells was previously suggested by D. Gabrilovich. From the migratory viewpoint, we are suggesting a more complex setup. It starts with crosstalk between the tumor site and the hematopoietic stem and progenitor cells (HSPCs) at the bone marrow (BM) and secondary lymphatic organs, resulting in rapid myelopoiesis followed by mobilization to the blood. Although myelopoiesis is coordinated by several cytokines and transcription factors, mobilization is selectively directed by chemokine receptors and may differ between M-MDSC and PMN-MDSC. These myeloid cells may then undergo further expansion at these secondary lymphatic organs and then home to the tumor site. Finally, selective homing of T cell subsets has been associated with retention at the target organs directed by adhesion molecules or chemokine receptors. The possible relevance to myeloid cells is still speculative but is discussed.https://www.frontiersin.org/articles/10.3389/fimmu.2020.557586/fullCCR5CCR2 chemokinescancermyeloid derived suppressor cellschemokine |
| spellingShingle | Nathan Karin The Development and Homing of Myeloid-Derived Suppressor Cells: From a Two-Stage Model to a Multistep Narrative Frontiers in Immunology CCR5 CCR2 chemokines cancer myeloid derived suppressor cells chemokine |
| title | The Development and Homing of Myeloid-Derived Suppressor Cells: From a Two-Stage Model to a Multistep Narrative |
| title_full | The Development and Homing of Myeloid-Derived Suppressor Cells: From a Two-Stage Model to a Multistep Narrative |
| title_fullStr | The Development and Homing of Myeloid-Derived Suppressor Cells: From a Two-Stage Model to a Multistep Narrative |
| title_full_unstemmed | The Development and Homing of Myeloid-Derived Suppressor Cells: From a Two-Stage Model to a Multistep Narrative |
| title_short | The Development and Homing of Myeloid-Derived Suppressor Cells: From a Two-Stage Model to a Multistep Narrative |
| title_sort | development and homing of myeloid derived suppressor cells from a two stage model to a multistep narrative |
| topic | CCR5 CCR2 chemokines cancer myeloid derived suppressor cells chemokine |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2020.557586/full |
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