Myeloid-derived suppressor cell role in tumor-related inflammation

Dolcetti, Luigi; Marigo, Ilaria; Mantelli, Barbara; Peranzoni, Elisa; Zanovello, Paola; Bronte, Vincenzo

doi:10.1016/j.canlet.2008.03.012

Cited by 104 publications

(69 citation statements)

References 98 publications

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“…The suppressive subsets thus appear to be very similar to Gr-1 int and Gr-1 low subsets described in our manuscript, suggesting common features of immunoregulatory myeloid cells expanded under different pathological situations [28]. TDSF comprise a wide variety of signaling molecules driving myelopoiesis [29,30]. Our data suggest that GM-CSF functions as a dominant factor promoting immunosuppressive pathways within the macro-population of CD11b 1 cells.…”

Section: Discussionsupporting

confidence: 79%

“…Transgenic mice on a BALB/c background expressing a K d -restricted HA 512-520 peptide-specific a/b TCR (CL4 mice) were a gift from L. Sherman (The Scripps Research Institute, La Jolla, CA, USA); pmel-1 TCR transgenic mice on a C57BL/6 background that express the Va1Vb13 TCR and specifically recognize the H-2D b restricted mouse and human gp100 [25][26][27][28][29][30][31][32][33] [34] were a gift from N. Restifo (Surgery Branch, National Institutes of Heath, Bethesda, MD, USA).…”

Section: Micementioning

confidence: 99%

“…MLPC were set up using 6 Â 10 5 BALB/c splenocytes together with 1% HA-specific CD8 1 T lymphocytes, derived from the spleen of CL4 transgenic mice (bearing a HA 512-520 peptidespecific TCR in CD8 1 T cells), pulsed with 1 mg/mL HA 512-520 peptide for 5 days. Alternatively, MLPC were set up with C57BL/ 6, instead of BALB/c, splenocytes together with 2% gp100 specific CD8 1 T lymphocytes, derived from the spleen of pmel-1 mice (bearing a hgp100 [25][26][27][28][29][30][31][32][33] peptide-specific TCR in CD8 1 T cells), pulsed with 1 mg/mL gp100 peptide for 5 days.…”

Section: Ctl Assaymentioning

confidence: 99%

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Hierarchy of immunosuppressive strength among myeloid‐derived suppressor cell subsets is determined by GM‐CSF

et al. 2009

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CD11b+/Gr‐1+ myeloid‐derived suppressor cells (MDSC) contribute to tumor immune evasion by restraining the activity of CD8+ T‐cells. Two major MDSC subsets were recently shown to play an equal role in MDSC‐induced immune dysfunctions: monocytic‐ and granulocytic‐like. We isolated three fractions of MDSC, i.e. CD11b+/Gr‐1high, CD11b+/Gr‐1int, and CD11b+/Gr‐1low populations that were characterized morphologically, phenotypically and functionally in different tumor models. In vitro assays showed that CD11b+/Gr‐1int cell subset, mainly comprising monocytes and myeloid precursors, was always capable to suppress CD8+ T‐cell activation, while CD11b+/Gr‐1high cells, mostly granulocytes, exerted appreciable suppression only in some tumor models and when present in high numbers. The CD11b+/Gr‐1int but not CD11b+/Gr‐1high cells were also immunosuppressive in vivo following adoptive transfer. CD11b+/Gr‐1low cells retained the immunosuppressive potential in most tumor models. Gene silencing experiments indicated that GM‐CSF was necessary to induce preferential expansion of both CD11b+/Gr‐1int and CD11b+/Gr‐1low subsets in the spleen of tumor‐bearing mice and mediate tumor‐induced tolerance whereas G‐CSF, which preferentially expanded CD11b+/Gr‐1high cells, did not create such immunosuppressive environment. GM‐CSF also acted on granulocyte–macrophage progenitors in the bone marrow inducing local expansion of CD11b+/Gr‐1low cells. These data unveil a hierarchy of immunoregulatory activity among MDSC subsets that is controlled by tumor‐released GM‐CSF.

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Section: Discussionsupporting

confidence: 79%

Section: Micementioning

confidence: 99%

Section: Ctl Assaymentioning

confidence: 99%

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Hierarchy of immunosuppressive strength among myeloid‐derived suppressor cell subsets is determined by GM‐CSF

et al. 2009

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“…The expansion of myeloid progenitor cells in these chimeras is reminiscent of the myeloid-derived suppressor cells described in association with myelosuppression, GvHD, tumors and chronic infections 21,29 where they have been implicated in tumor-specific and nonspecific T-cell dysfunction. [30][31][32] Our earlier data, 21 and more recently those of others, 33 suggest that these cells may have a role in controlling GvH reactivity. Whether they contribute in this model to confining GvH reactivity to the lymphohematopoietic system is the subject of ongoing investigations.…”

Section: Discussionmentioning

confidence: 68%

Subclinical GvHD in non-irradiated F1 hybrids: severe lymphoid-tissue GvHD causing prolonged immune dysfunction

Sprangers

Wijmeersch

Luyckx

et al. 2010

Bone Marrow Transplant

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GvHD is an important complication of allogeneic hematopoietic SCT. Parent-in-F1 models are frequently used to study GvHD immunobiology; the characteristics of parent-in-F1 GvHD vary between strain combinations and induction protocols. Here, we observed that a high-dose challenge of non-irradiated B6DBA2F1 and B6SJLF1 recipients with C57BL/6 splenocytes left the majority of recipients clinically healthy, while inducing progressive high-grade donor T-cell chimerism. We investigated this previously undescribed pattern of parent-in-F1 T-cell alloreactivity and studied the effect of serial parental splenocyte infusions on epithelial and lymphohematopoietic tissues. The majority of recipients of 4 weekly splenocyte infusions showed long-term survival with gradual establishment of high-grade donor chimerism and without any signs of epithelial-tissue GvHD. A minority of recipients showed BM failure type of GvHD and, respectively, graft rejection. Moreover, long-term F1 chimeras showed protracted pancytopenia, and in peripheral lymphoid tissues severe lymphopenia and near-complete eradication of APCs and dysfunction in antigen-presenting capacity in remaining APC. Hematopoiesis and lymphoid tissue composition recovered only after multilineage donor chimerism had established. In conclusion, we report on a novel type of parent-in-F1 hybrid GvHD, where a cumulative high dose of C57BL/6 parental splenocytes in non-irradiated F1 mice induces subclinical but severe hematolymphoid-tissue GvHD, causing prolonged immuno-incompetence.

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“…Natural killer cells (NKs) of innate immunity eradicate cells by inducing cytotoxicity through the release of perforin and granzyme that target the cell to destruction by apoptosis, while NKT cells share similarities with T cells, with recognition of lipid and glycolipid antigens. A subset of early myeloid cells termed myeloid derived suppressor cells (MDSCs) has the ability to suppress NK, NKT, and T cell responses, marked by production of L-arginine and upregulation of nitric oxide synthase 2 (Dolcetti et al, 2008).…”

Section: Inflammatory Cellsmentioning

confidence: 99%

Immunotherapy in Urologic Malignancies: The Evolution and Future of Pattern Recognition Receptors

Lee¹,

Chin²

2012

Advancements in Tumor Immunotherapy and Cancer Vaccines

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Myeloid-derived suppressor cell role in tumor-related inflammation

Cited by 104 publications

References 98 publications

Hierarchy of immunosuppressive strength among myeloid‐derived suppressor cell subsets is determined by GM‐CSF

Hierarchy of immunosuppressive strength among myeloid‐derived suppressor cell subsets is determined by GM‐CSF

Subclinical GvHD in non-irradiated F1 hybrids: severe lymphoid-tissue GvHD causing prolonged immune dysfunction

Immunotherapy in Urologic Malignancies: The Evolution and Future of Pattern Recognition Receptors

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