Distinct myeloid suppressor cell subsets correlate with plasma IL-6 and IL-10 and reduced interferon-alpha signaling in CD4+ T cells from patients with GI malignancy

Mundy-Bosse, Bethany L.; Young, Gregory S.; Bauer, Todd M.; Binkley, Elaine M.; Bloomston, Mark; Bill, Matthew A.; Bekaii‐Saab, Tanios; Carson, William E.; Lesinski, Gregory B.

doi:10.1007/s00262-011-1029-z

Cited by 117 publications

(125 citation statements)

References 52 publications

Supporting

Mentioning

119

Contrasting

Order By: Relevance

“…The systemic increase of IL-6 levels in the plasma of patients with cancer (28,29) markedly correlated with proportional accumulation of MDSC (30,31). These reports support our findings and previous reports (39,40) that MDSC produce IL-6 in tumor-bearing mice.…”

Section: Discussionsupporting

confidence: 82%

“…Chronic inflammation and increased levels of inflammatory cytokines including IL-6 have been reported in patients with various type of tumors (26), and an elevated level of IL-6 fostering progressive expansion of tumor cells (27) has been associated with poor clinical outcome (28)(29)(30)(31). Here, we focused on the association between the functional impairment of CD4 þ T cells and immune-suppressive effects of the tumor-induced inflammation-related factors, IL-6 and MDSC.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Myeloid-Derived Suppressor Cells Attenuate TH1 Development through IL-6 Production to Promote Tumor Progression

Tsukamoto

Nishikata

Senju

et al. 2013

Cancer Immunology Research

View full text Add to dashboard Cite

Collaborative action between tumor cells and host-derived suppressor cells leads to peripheral tolerance of T cells to tumor antigens. Here, we showed that in tumor-bearing mice, generation of tumor antigen-specific effector T-helper cells (T H 1) was significantly attenuated, and impaired T H 1 differentiation was restored by the temporal blockade of interleukin (IL)-6 activity at the T-cell priming phase. Furthermore, we found that Gr-1 þ myeloid-derived suppressor cells (MDSC) served as a source of IL-6 in tumor-bearing mice. Adoptive transfer of effector CD4 þ T cells revealed that MDSC-sensitized effector CD4 þ T cells were less potent in mounting antitumor immune responses, although effector T cells generated together with Gr-1 þ cells from tumor-free mice eradicated established tumors. CD8 þ T cells, IFN-g, and MHC-class II expression in host mice were indispensable for the antitumor activity initiated by effector CD4 þ T cells. Despite comparable suppressive activity of IL-6 þ/þ and IL-6 À/À MDSC on primary T-cell activation, transfer of IL-6 þ/þ MDSC, but not IL-6 À/À MDSC, dampened the efficient induction of effector T H 1 cells and counteracted CD4 þ T cell-mediated antitumor immunity including cognate help for CD8 þ T cells in vivo. These findings suggest that, apart from the inhibitory effects on primary T-cell activation, MDSC promote tumor progression by attenuating functional differentiation of tumor-specific CD4 þ T cells into effector T H 1 cells through IL-6 production to promote tumor progression. This novel mode of MDSC-induced tolerance of effector CD4 þ T cells should be considered as the basis for the rational design of effective T cell-mediated antitumor therapies.

show abstract

Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Myeloid-Derived Suppressor Cells Attenuate TH1 Development through IL-6 Production to Promote Tumor Progression

Tsukamoto

Nishikata

Senju

et al. 2013

Cancer Immunology Research

View full text Add to dashboard Cite

show abstract

“…In contrast to murine MDSCs, which are defined by the expression of Gr-1 and CD11b, the corresponding cells in humans are inadequately characterized due to the lack of uniform markers. MDSCs have been intensively studied in cancer and were found to have important implications in disease progression (38)(39)(40). To investigate the MDSCs, we chose 2 subsets of markers that have shown statistical association with human cancer disease stages (38)(39)(40).…”

Section: Discussionmentioning

confidence: 99%

Vaccine-induced myeloid cell population dampens protective immunity to SIV

et al. 2014

View full text Add to dashboard Cite

Vaccines are largely evaluated for their ability to promote adaptive immunity, with little focus on the induction of negative immune regulators. Adjuvants facilitate and enhance vaccine-induced immune responses and have been explored for mediating protection against HIV. Using a regimen of peptide priming followed by a modified vaccinia Ankara (MVA) boost in a nonhuman primate model, we found that an SIV vaccine incorporating molecular adjuvants mediated partial protection against rectal SIVmac251 challenges. Animals treated with vaccine and multiple adjuvants exhibited a reduced viral load (VL) compared with those treated with vaccine only. Surprisingly, animals treated with adjuvant alone had reduced VLs that were comparable to or better than those of the vaccine-treated group. VL reduction was greatest in animals with the MHC class I allele Mamu-A*01 that were treated with adjuvant only and was largely dependent on CD8 + T cells. Early VLs correlated with Ki67 + CCR5 + CD4 + T cell frequency, while set-point VL was associated with expansion of a myeloid cell population that was phenotypically similar to myeloid-derived suppressor cells (MDSCs) and that suppressed T cell responses in vitro. MDSC expansion occurred in animals receiving vaccine and was not observed in the adjuvant-only group. Collectively, these results indicate that vaccine-induced MDSCs inhibit protective cellular immunity and suggest that preventing MDSC induction may be critical for effective AIDS vaccination.

show abstract

“…Elevated IL-6 levels have been found to correlate with increased MDSC frequencies and suppressive functions in tumor-bearing hosts [48,78]. It has been shown that IL-6 mediated the generation, migration and activation of MDSCs via transcription factor STAT3 [26,33,79].…”

Section: General Characteristic Of Mdscsmentioning

confidence: 99%

Tumor Microenvironment and Myeloid-Derived Suppressor Cells

Umansky

Sevko

2012

Cancer Microenvironment

118

View full text Add to dashboard Cite

Tumor progression has been demonstrated to be supported by chronic inflammatory conditions developed in the tumor microenvironment and characterized by the longterm secretion of various inflammatory soluble factors (including cytokines, chemokines, growth factors, reactive oxygen and nitrogen species, prostaglandins etc.) and strong leukocyte infiltration. Among leukocytes infiltrating tumors, myeloid-derived suppressor cells (MDSCs) represent one of the most important players mediating immunosuppression. These cells may not only strongly inhibit an anti-tumor immune reactions mediated by T cells but also directly stimulate tumorigenesis, tumor growth and metastasis by enhancing neoangiogenesis and creating a suitable environment for the metastatic formation. This review provides an overview of interactions between MDSCs and tumor cells leading to MDSC generation, activation and migration to the tumor site, where they can strongly enhance tumor progression. Better understanding of the MDSC-tumor interplay is critical for the development of new strategies of tumor immunotherapy.

show abstract

Distinct myeloid suppressor cell subsets correlate with plasma IL-6 and IL-10 and reduced interferon-alpha signaling in CD4+ T cells from patients with GI malignancy

Cited by 117 publications

References 52 publications

Myeloid-Derived Suppressor Cells Attenuate TH1 Development through IL-6 Production to Promote Tumor Progression

Myeloid-Derived Suppressor Cells Attenuate TH1 Development through IL-6 Production to Promote Tumor Progression

Vaccine-induced myeloid cell population dampens protective immunity to SIV

Tumor Microenvironment and Myeloid-Derived Suppressor Cells

Contact Info

Product

Resources

About