CD34+ Immune Suppressive Cells in the Peripheral Blood of Patients with Head and Neck Cancer

Pandit, Rajiv; Dm, Lathers; Nm, Beal; Garrity, Thomas; Mr, Young

doi:10.1177/000348940010900809

Cited by 38 publications

(35 citation statements)

References 25 publications

(15 reference statements)

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“…However, knowledge of MDSC is primarily based on preclinical work, and to date only few published studies have involved cancer patients [1,11,19,23,30]. Considering the importance of MDSC as an important mechanism of cancer immune-evasion, more definitive human studies are needed.…”

Section: Discussionmentioning

confidence: 99%

“…Consequently few published studies to date have investigated the clinical significance of MDSC [1,11,19,23,30]. To date the most comprehensive work in cancer patients established that MDSC were double negative for the MHC class II molecule (HLA DR) and any other surface markers of mature lymphoid or myeloid cells (CD3, CD19, CD57, CD14) or Lin −/Lo [1,2].…”

Section: Introductionmentioning

confidence: 99%

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Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin–cyclophosphamide chemotherapy

Díaz-Montero

Salem

Nishimura

et al. 2008

Cancer Immunol Immunother

1,095

889

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Abnormal accumulation of myeloid-derived suppressor cells (MDSC) is an important mechanism of tumor immune evasion. Cyclophosphamide (CTX) has also been shown in non-tumor bearing animals to cause transient surges in MDSC. Knowledge of MDSC is primarily based on preclinical work, and to date only few published studies have involved cancer patients. The goal of this study was to test the hypothesis that circulating MDSC levels correlate with clinical cancer stage, CTX-based chemotherapy, and metastatic tumor burden. Whole blood was collected from 106 newly diagnosed solid tumor patients (stages I-IV). Percentages of circulating MDSC (Lin −/Lo , HLA DR−, CD33 + CD11b + ) were determined prior to initiation of systemic therapy. In 17 early stage breast cancer patients receiving doxorubicin-cyclophosphamide chemotherapy every 14 days (ddAC) blood was collected on day 1 of each cycle. Circulating MDSC were significantly increased in cancer patients of all stages relative to healthy volunteers. A significant correlation between circulating MDSC and clinical cancer stage was also observed. Moreover, among stage IV patients, those with extensive metastatic tumor burden had the highest percent and absolute number of MDSC. Significant increases in circulating MDSC were observed with ddAC NIH Public AccessAuthor Manuscript Cancer Immunol Immunother. Author manuscript; available in PMC 2012 July 23.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin–cyclophosphamide chemotherapy

Díaz-Montero

Salem

Nishimura

et al. 2008

Cancer Immunol Immunother

1,095

889

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“…Key Words: CD8 + T cells, CD11b, cyclophosphamide, dsRNA, dendritic cells, IFN, Ly6G, myeloid cells, OVA, OT-1 T cells, poly (I:C), TLR3, vaccine (J Immunother 2007;30: [40][41][42][43][44][45][46][47][48][49][50][51][52][53] A critical component of antitumor immunity is the development of effector T cells that can survive longterm as functional memory T cells. It is currently believed that naive T cells are programmed to expand dramatically after antigen encounter.…”

mentioning

confidence: 99%

Defining the Ability of Cyclophosphamide Preconditioning to Enhance the Antigen-specific CD8+ T-cell Response to Peptide Vaccination: Creation of a Beneficial Host Microenvironment Involving Type I IFNs and Myeloid Cells

Salem

Kadima

El‐Naggar

et al. 2007

Journal of Immunotherapy

104

123

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Although cyclophosphamide (CTX) has been clearly shown to enhance active specific and adoptive immunotherapies, the mechanism(s) underlying these beneficial effects have not been clearly defined. To define the impact of CTX preconditioning on the antigen-specific CD8 T-cell response to peptide vaccination, we used an adoptive transfer model based on the OT-1 T-cell receptor transgenic mouse. CTX preconditioning dramatically enhanced the antigen-specific CD8 T-cell response to peptide vaccination. Specifically, CTX significantly enhanced the expansion and function of responding CD8 T cells as demonstrated by flow cytometry and cytokine production. In parallel experiments, we attempted to define the mechanism(s) underlying these beneficial effects of CTX therapy. CTX therapy increased the relative number and activation status of myeloid dendritic cells, and was associated with the induction of significant levels of the inflammatory cytokines interferon-a, monocyte chemoattractant protein-1, and IL-6. Adoptive transfer experiments into type I IFNR À / À and CR3 À / À mice confirmed that the beneficial effects of CTX were at least partially dependent on type I interferons and myeloid cells. Adoptive transfer of up to 150 Â 10 6 naive spleen cells at the time of antigen-specific CD8 T-cell transfer did not abrogate the effects of CTX therapy, suggesting that the creation of a niche in the immune system may not be required. CTX decreased the absolute, but not relative number of CD4 + CD25 + T reg cells, consistent with the possibility that regulatory T cells may be targeted by CTX therapy. Of note, combination therapy with CTX and a synthetic TLR3 agonist further enhanced the antigen-specific CD8 + T-cell response. Taken together, our data suggest that CTX modulates specific components of the innate immune system resulting in a beneficial host microenvironment. Specific targeting of these components may enhance the effectiveness of CTX preconditioning for adoptive immunotherapy.A critical component of antitumor immunity is the development of effector T cells that can survive longterm as functional memory T cells. It is currently believed that naive T cells are programmed to expand dramatically after antigen encounter. This expansion phase is followed by a significant contraction phase in which the majority of antigen-specific T cells undergo apoptosis, leaving behind only a small population of memory T cells. 1 It is becoming increasing clear, however, that the state of the host environment at the time of antigen encounter can substantially impact on this CD8 program, affecting the number and quality of effector and memory T cells. [2][3][4][5][6] In this context, it has been reported that conditioning of the recipient host with chemotherapeutic agents before adoptive T-cell transfer can potentiate the efficacy of active specific and adoptive immunotherapies. 7 Cyclophosphamide (CTX) is a chemotherapeutic agent used for the treatment of several human malignancies, often in combination with adoptive immunotherapy. 7-9 A...

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“…This is in part due to tissue infiltration by immunosuppressive immature progenitor cells with surface marker CD34 39,40 . In one study, HNSCC patients treated with 1,25(OH) 2 D 3 exhibited decreased levels of intratumoral CD34 + cell populations and diminished the preexisting profound immunoinhibitory effect of the cancer.…”

Section: Immune Escapementioning

confidence: 99%

Vitamin D3 and Its Role in the Treatment of Head and Neck Squamous Cell Carcinoma

Young¹,

Walker²

2012

Squamous Cell Carcinoma

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CD34+ Immune Suppressive Cells in the Peripheral Blood of Patients with Head and Neck Cancer

Cited by 38 publications

References 25 publications

Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin–cyclophosphamide chemotherapy

Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin–cyclophosphamide chemotherapy

Defining the Ability of Cyclophosphamide Preconditioning to Enhance the Antigen-specific CD8+ T-cell Response to Peptide Vaccination: Creation of a Beneficial Host Microenvironment Involving Type I IFNs and Myeloid Cells

Vitamin D3 and Its Role in the Treatment of Head and Neck Squamous Cell Carcinoma

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