TNF neutralization results in the delay of transplantable tumor growth and reduced MDSC accumulation.
Myeloid-derived suppressor cells (MDSC) represent a heterogeneous population of immature myeloid cells that under normal conditions may differentiate into mature macrophages, granulocytes and dendritic cells. However, under pathological conditions associated with inflammation, cancer or infection su...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2016-04-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fimmu.2016.00147/full |
| _version_ | 1828498167340990464 |
|---|---|
| author | Kamar-Sulu N. Atretkhany Kamar-Sulu N. Atretkhany Maxim A. Nosenko Maxim A. Nosenko Maxim A. Nosenko Violetta S. Gogoleva Violetta S. Gogoleva Ruslan V. Zvartsev Zhihai eQin Sergei A. Nedospasov Sergei A. Nedospasov Sergei A. Nedospasov Marina S. Drutskaya |
| author_facet | Kamar-Sulu N. Atretkhany Kamar-Sulu N. Atretkhany Maxim A. Nosenko Maxim A. Nosenko Maxim A. Nosenko Violetta S. Gogoleva Violetta S. Gogoleva Ruslan V. Zvartsev Zhihai eQin Sergei A. Nedospasov Sergei A. Nedospasov Sergei A. Nedospasov Marina S. Drutskaya |
| author_sort | Kamar-Sulu N. Atretkhany |
| collection | DOAJ |
| description | Myeloid-derived suppressor cells (MDSC) represent a heterogeneous population of immature myeloid cells that under normal conditions may differentiate into mature macrophages, granulocytes and dendritic cells. However, under pathological conditions associated with inflammation, cancer or infection such differentiation is inhibited leading to immature myeloid cell expansion. Under the influence of inflammatory cytokines, these cells become MDSC, acquire immunosuppressive phenotype and accumulate in the affected tissue, as well as in the periphery. Immune suppressive activity of MDSC is partly due to upregulation of arginase 1 (Arg1), inducible nitric oxide synthase (iNOS) and anti-inflammatory cytokines, such as IL-10 and TGF-β. These suppressive factors can enhance tumor growth by repressing T-cell-mediated anti-tumor responses. TNF is a critical factor for induction, expansion and suppressive activity of MDSC. In this study we evaluated the effects of systemic TNF ablation on tumor-induced expansion of MDSC in vivo using TNF humanized (hTNF KI) mice. Both Etanercept and Infliximab treatments resulted in a delayed growth of MCA 205 fibrosarcoma in hTNF KI mice, significantly reduced tumor volume and in less accumulated MDSC in the blood three weeks after tumor cell inoculation. Thus, our study uncovers anti-tumor effects of systemic TNF ablation in vivo. |
| first_indexed | 2024-12-11T13:02:15Z |
| format | Article |
| id | doaj.art-b1d17e45fd974b40a01de3fa0b896789 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T13:02:15Z |
| publishDate | 2016-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-b1d17e45fd974b40a01de3fa0b8967892022-12-22T01:06:27ZengFrontiers Media S.A.Frontiers in Immunology1664-32242016-04-01710.3389/fimmu.2016.00147185812TNF neutralization results in the delay of transplantable tumor growth and reduced MDSC accumulation.Kamar-Sulu N. Atretkhany0Kamar-Sulu N. Atretkhany1Maxim A. Nosenko2Maxim A. Nosenko3Maxim A. Nosenko4Violetta S. Gogoleva5Violetta S. Gogoleva6Ruslan V. Zvartsev7Zhihai eQin8Sergei A. Nedospasov9Sergei A. Nedospasov10Sergei A. Nedospasov11Marina S. Drutskaya12Engelhardt Institute of Molecular BiologyImmunolgy Department, Faculty of Biology, and Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State UniversityEngelhardt Institute of Molecular BiologyImmunolgy Department, Faculty of Biology, and Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State UniversityGerman Rheumatology Research Center (DRFZ)Engelhardt Institute of Molecular BiologyImmunolgy Department, Faculty of Biology, and Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State UniversityEngelhardt Institute of Molecular BiologyInstitute of Biophysics, Chinese Academy of SciencesEngelhardt Institute of Molecular BiologyImmunolgy Department, Faculty of Biology, and Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State UniversityGerman Rheumatology Research Center (DRFZ)Engelhardt Institute of Molecular BiologyMyeloid-derived suppressor cells (MDSC) represent a heterogeneous population of immature myeloid cells that under normal conditions may differentiate into mature macrophages, granulocytes and dendritic cells. However, under pathological conditions associated with inflammation, cancer or infection such differentiation is inhibited leading to immature myeloid cell expansion. Under the influence of inflammatory cytokines, these cells become MDSC, acquire immunosuppressive phenotype and accumulate in the affected tissue, as well as in the periphery. Immune suppressive activity of MDSC is partly due to upregulation of arginase 1 (Arg1), inducible nitric oxide synthase (iNOS) and anti-inflammatory cytokines, such as IL-10 and TGF-β. These suppressive factors can enhance tumor growth by repressing T-cell-mediated anti-tumor responses. TNF is a critical factor for induction, expansion and suppressive activity of MDSC. In this study we evaluated the effects of systemic TNF ablation on tumor-induced expansion of MDSC in vivo using TNF humanized (hTNF KI) mice. Both Etanercept and Infliximab treatments resulted in a delayed growth of MCA 205 fibrosarcoma in hTNF KI mice, significantly reduced tumor volume and in less accumulated MDSC in the blood three weeks after tumor cell inoculation. Thus, our study uncovers anti-tumor effects of systemic TNF ablation in vivo.http://journal.frontiersin.org/Journal/10.3389/fimmu.2016.00147/fullPro-inflammatory cytokinesTNFIL-6MDSCAnti-cytokine therapytransplantable tumor model |
| spellingShingle | Kamar-Sulu N. Atretkhany Kamar-Sulu N. Atretkhany Maxim A. Nosenko Maxim A. Nosenko Maxim A. Nosenko Violetta S. Gogoleva Violetta S. Gogoleva Ruslan V. Zvartsev Zhihai eQin Sergei A. Nedospasov Sergei A. Nedospasov Sergei A. Nedospasov Marina S. Drutskaya TNF neutralization results in the delay of transplantable tumor growth and reduced MDSC accumulation. Frontiers in Immunology Pro-inflammatory cytokines TNF IL-6 MDSC Anti-cytokine therapy transplantable tumor model |
| title | TNF neutralization results in the delay of transplantable tumor growth and reduced MDSC accumulation. |
| title_full | TNF neutralization results in the delay of transplantable tumor growth and reduced MDSC accumulation. |
| title_fullStr | TNF neutralization results in the delay of transplantable tumor growth and reduced MDSC accumulation. |
| title_full_unstemmed | TNF neutralization results in the delay of transplantable tumor growth and reduced MDSC accumulation. |
| title_short | TNF neutralization results in the delay of transplantable tumor growth and reduced MDSC accumulation. |
| title_sort | tnf neutralization results in the delay of transplantable tumor growth and reduced mdsc accumulation |
| topic | Pro-inflammatory cytokines TNF IL-6 MDSC Anti-cytokine therapy transplantable tumor model |
| url | http://journal.frontiersin.org/Journal/10.3389/fimmu.2016.00147/full |
| work_keys_str_mv | AT kamarsulunatretkhany tnfneutralizationresultsinthedelayoftransplantabletumorgrowthandreducedmdscaccumulation AT kamarsulunatretkhany tnfneutralizationresultsinthedelayoftransplantabletumorgrowthandreducedmdscaccumulation AT maximanosenko tnfneutralizationresultsinthedelayoftransplantabletumorgrowthandreducedmdscaccumulation AT maximanosenko tnfneutralizationresultsinthedelayoftransplantabletumorgrowthandreducedmdscaccumulation AT maximanosenko tnfneutralizationresultsinthedelayoftransplantabletumorgrowthandreducedmdscaccumulation AT violettasgogoleva tnfneutralizationresultsinthedelayoftransplantabletumorgrowthandreducedmdscaccumulation AT violettasgogoleva tnfneutralizationresultsinthedelayoftransplantabletumorgrowthandreducedmdscaccumulation AT ruslanvzvartsev tnfneutralizationresultsinthedelayoftransplantabletumorgrowthandreducedmdscaccumulation AT zhihaieqin tnfneutralizationresultsinthedelayoftransplantabletumorgrowthandreducedmdscaccumulation AT sergeianedospasov tnfneutralizationresultsinthedelayoftransplantabletumorgrowthandreducedmdscaccumulation AT sergeianedospasov tnfneutralizationresultsinthedelayoftransplantabletumorgrowthandreducedmdscaccumulation AT sergeianedospasov tnfneutralizationresultsinthedelayoftransplantabletumorgrowthandreducedmdscaccumulation AT marinasdrutskaya tnfneutralizationresultsinthedelayoftransplantabletumorgrowthandreducedmdscaccumulation |