Human squamous cell carcinomas of the head and neck chemoattract immune suppressive CD34+ progenitor cells

Young, Matthew R.; Petruzzelli, Guy J.; Kolesiak, Kristin; Achille, Nicholas J.; Lathers, Deanne; Gabrilovich, Dmitry I.

doi:10.1016/s0198-8859(01)00222-1

Cited by 78 publications

(38 citation statements)

References 30 publications

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“…In healthy mice, Gr1 ϩ CD11b ϩ cells differentiate into these normal cell types. However, under chronic inflammatory conditions 1 during periods of stress, 36 in aged persons, 37 and in persons with infections, 38 cancer, 39,40 or autoimmunity, 41 MDSC levels are elevated. Proinflammatory mediators such as IL-1␤, 11,12 PGE 2 , 14,15 IL-6, 13,42 complement component C5a, 43 VEGF, 20 and GM-CSF 17 are inducers of MDSCs.…”

Section: Discussionmentioning

confidence: 99%

Myeloid-derived suppressor cells express the death receptor Fas and apoptose in response to T cell–expressed FasL

Sinha

Chornoguz

Clements

et al. 2011

Blood

142

119

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IntroductionTumor progression in patients and mice is associated with increasing levels of a population of suppressor cells known as myeloidderived suppressor cells (MDSCs). MDSCs suppress antitumor immunity by blocking the activation of CD4 ϩ and CD8 ϩ T cells, 1-3 skewing cytokine production toward a type 2 phenotype, 4 inhibiting natural killer-cell cytotoxicity, 5,6 promoting the accumulation of immune suppressive regulatory T cells, 7,8 and perturbing lymphocyte trafficking. 9 As a result, MDSCs are a significant obstacle to cancer immunotherapies that require activation of the host's immune system.A hallmark of tumor-driven MDSCs is their elevated presence in the BM, spleen, blood, lymph nodes, and primary and metastatic tumor sites. 1,10 Their accumulation is attributed to multiple proinflammatory factors, including IL-1␤, 11,12 IL-6, 13 prostaglandin E 2 (PGE 2 ), 14,15 S100A8/A9 proteins, 10, 17 and VEGF,18,19 driving their differentiation from hemopoietic progenitor cells. These inflammatory mediators are produced by tumor cells 13,[20][21][22] or host cells 23,24 or both. In persons with cancer, tumor cells are the predominant inducers because removal of tumor causes a rapid decrease in MDSCs. 25,26 In contrast to induction of MDSCs, the factors that regulate MDSC maintenance and turnover are not well understood.Accumulation For personal use only. on May 11, 2018. by guest www.bloodjournal.org From Mass spectrometryMDSCs were obtained from the peripheral blood of tumor-bearing mice 14 (Ͼ 90% Gr1 ϩ CD11b ϩ cells; 5 ϫ 10 6 -10 7 cells/mouse) and lysed at a final concentration of 0.1% Rapigest acid-cleavable detergent (Waters) in 100mM NH 4 HCO 3 , pH 8.4. Cell lysates were digested with sequencing grade-modified trypsin (1:50 trypsin-to-protein ratio; Promega) for 1 hour at 37°C, after which trifluoroacetic acid was added to a final pH of ϳ 3. Lysates were incubated for 1 hour at 37°C, freeze-thawed at Ϫ80°C, and microfuged at 13 200 rpm for 5 minutes (Eppendorf 5415 D), and the trifluoroacetic acid-precipitated material was discarded. 27 Supernatant fluid containing tryptic peptides was collected and brought to pH 7, and peptide concentration was measured by OD 280. Peptides (30 g) were desalted (C18 spin cartridges; Pierce) and analyzed with a LTQ-FT Ultra mass spectrometer (ThermoFischer) interfaced with an Agilent 1100 nanoLC system. Tandem mass spectra were searched against the National Center for Biotechnology Information (NCBI) mouse protein database 28 with the use of MASCOT data analysis software (v2.1; Matrix Science) with the following conditions: peptide mass tolerance at 10 ppm; fragment mass tolerance at 1.5 Da; a maximum of 2 allowed missed cleavages; and methionine oxidation and disulfide as the variable modifications. Proteins identified by Ն 2 peptides with a MASCOT MOWSE (molecular weight search) score Ͼ 30 were considered reliable identifications. 29 Antibodies, flow cytometry, confocal microscopyFluorescently coupled mAbs to Gr1, CD11b, Fas, FasL, CD69, CD3, CD4, DO11.10 TCR (clon...

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Section: Discussionmentioning

confidence: 99%

Myeloid-derived suppressor cells express the death receptor Fas and apoptose in response to T cell–expressed FasL

Sinha

Chornoguz

Clements

et al. 2011

Blood

142

119

View full text Add to dashboard Cite

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“…6, 7). MDSCs are found in increased levels in the blood of patients diagnosed with different cancer types, including head and neck, breast, non-small cell lung, renal, pancreatic, esophageal, gastric cancers, and melanoma (8)(9)(10)(11)(12). MDSCs, a heterogeneous population of immature myeloid cells, are capable of interfering with tumor immunity and promoting tumor growth by inhibiting natural killer (NK) cell cytotoxicity and CD4 þ and CD8 þ T-cell activation, as well as the activation and attraction of regulatory T cells (Treg), but their actual contribution in the performance of anticancer vaccines is largely unknown (13)(14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

Protection against HPV-16–Associated Tumors Requires the Activation of CD8+ Effector Memory T Cells and the Control of Myeloid-Derived Suppressor Cells

Diniz

Sales

Silva

et al. 2016

Molecular Cancer Therapeutics

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“…[9][10][11][12] An expansion of immature myeloid cells with immune suppressive capacity is evident in the peripheral blood (PB) of patients bearing tumors of various types. 13,14 Because a defective immune response allows tumors to evade host immune control, these issues assume importance in the immunotherapy of cancer. 15 Increased numbers of myeloid cells expressing the Gr-1 (Ly6G) and Mac-1 (CD11b) markers have been detected in the spleen and bone marrow (BM) of mice bearing transplantable tumors 12,[16][17][18][19][20] and in many conditions associated with impaired immune reactivity, such as cyclophosphamide treatment, 21 severe Trypanosoma infections, 22 lymphoid irradiation, and intensive immunization protocols.…”

Section: Introductionmentioning

confidence: 99%

Myeloid cell expansion elicited by the progression of spontaneous mammary carcinomas in c-erbB-2 transgenic BALB/c mice suppresses immune reactivity

Melani

Chiodoni

Forni

et al. 2003

Blood

261

207

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Transgenic female mice expressing the transforming rat oncogene c-erbB-2 (HER-2/neu) under the mouse mammary tumor virus (MMTV) promoter (BALB-neuT) spontaneously develop mammary carcinomas with a progression resembling that of human breast cancer. In these mice, activating antitumor immunotherapy fails to induce T cell-mediated cytotoxicity, suggesting a suppression of the immune response. We found a direct correlation between tumor multiplicity and an increased proportion of Gr-

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Human squamous cell carcinomas of the head and neck chemoattract immune suppressive CD34+ progenitor cells

Cited by 78 publications

References 30 publications

Myeloid-derived suppressor cells express the death receptor Fas and apoptose in response to T cell–expressed FasL

Myeloid-derived suppressor cells express the death receptor Fas and apoptose in response to T cell–expressed FasL

Protection against HPV-16–Associated Tumors Requires the Activation of CD8+ Effector Memory T Cells and the Control of Myeloid-Derived Suppressor Cells

Myeloid cell expansion elicited by the progression of spontaneous mammary carcinomas in c-erbB-2 transgenic BALB/c mice suppresses immune reactivity

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