Mechanisms of immune suppression in patients with head and neck cancer: Influence on the immune infiltrate of the cancer

Young, Matthew R.; Wright, M. A.; Lozano, Yvonne; Matthews, Janice R.; Benefield, Janet; Prechel, Margaret

doi:10.1002/(sici)1097-0215(19960729)67:3<333::aid-ijc5>3.0.co;2-s

Cited by 158 publications

(60 citation statements)

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“…Our prior studies showed presence of CD34 1 cells within HNSCC that secrete high levels of GM-CSF, and that these parameters were correlated with reduced levels of CD8 1 T-cells and reduced CD4 1 cell function by the tumor-infiltrating lymphocytes (Young et al, 1996b). In the present study, the possibility that this translated into a worsened outcome for the HNSCC cancer patients was assessed.…”

Section: Patient Profile and Data Analysismentioning

confidence: 71%

“…Fragments were either directly placed into culture for measurement of secreted GM-CSF, or were dissociated into single cell suspensions for flow cytometric analysis. To prepare single cell suspensions, cancer fragments were enzymatically dissociated as we previously described 1996b) by incubation for 2 hr in a mixture of 1 mg/ml collagenase type IV, 0.5 mg/ml hyaluronidase type V and 0.1 mg/ml DNase type 1 (Sigma, St. Louis, MO). Single cell suspensions of the dissociated cancers were centrifuged in a Ficoll-Hypaque gradient (1.077 gm/l), recovered from the interface, washed, immunostained, and FACS analyzed.…”

Section: Human Head and Neck Cancersmentioning

confidence: 99%

“…Dissociated HNSCC samples were stained by direct immunofluorescence using fluorescein (FITC)-CD34 antibody or a FITCisotype control (PharMingen, San Diego, CA) (Young et al, 1996b;. After 30 min of incubation on ice in the dark, the cells were washed and the percent positive staining cells was measured using a FACS 420 (Becton Dickinson, Sunnyvale, CA).…”

Section: Flow Cytometric Analysis Of Intratumoral Cd34 1 Cell Contentmentioning

confidence: 99%

“…In a murine tumor model, diminishing the levels of NS cells increases anti-tumor immune reactivity and reduces both tumor metastasis and recurrence Young et al, 1996a;Prechel et al, 1996). Analysis of over 200 human HNSCC specimens showed that cancers with a high frequency of CD34 1 cells have a lower CD8 1 cell content and reduced function of intratumoral CD4 1 cells (Young et al, 1996b).Despite indications that NS cells contribute to the immune dysfunction of HNSCC patients, studies have not assessed whether this translates into increased tumor metastasis or recurrence following tumor excision. The results of the present studies showed that GM-CSF production and CD34 1 cell content are higher in surgically excised primary tumors that subsequently recur or metastasize within 2 years, as compared with primary tumors that remained in remission for at least 2 years following excision.…”

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confidence: 99%

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Increased recurrence and metastasis in patients whose primary head and neck squamous cell carcinomas secreted granulocyte-macrophage colony-stimulating factor and contained CD34+ natural suppressor cells

et al. 1997

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Human head and neck squamous cell carcinomas (HNSCC) that produce high levels of granulocyte-macrophage colonystimulating factor (GM-CSF) have been shown to contain CD34 1 natural suppressor cells that inhibit the activity of intratumoral T-cells. The present study evaluated whether GM-CSF production and the presence of CD34 1 cells within primary HNSCC would translate into increased recurrence, metastasis or cancer-related death during the 2 years following surgical excision. Freshly excised primary HNSCC of 20 patients that subsequently developed disease, and of 17 patients that remained with no evidence of disease were analyzed for production of GM-CSF and for CD34 1 cell content. The cancers of patients that subsequently developed recurrences or metastatic disease produced almost 4-fold the levels of GM-CSF and had approximately 2.5-fold the number of CD34 1 cells as did cancers of patients that remained disease-free. In a second method of analysis, the prognostic significance of high vs. low GM-CSF and CD34 1 cell values was evaluated. These analyses showed that patients whose cancers produced high GM-CSF levels or had a high CD34 1 cell content had a disproportionately high incidence of recurrence or metastatic disease (94% and 100%, respectively), while the majority of patients whose primary cancers produced low levels of GM-CSF or had a low CD34 1 cell content remained disease-free (16% and 19%, respectively). Our results indicate that the presence of CD34 1 cells in GM-CSFproducing HNSCC is associated with a poorer prognosis for the cancer patients and suggest the utility of these parameters as prognostic indicators of outcome. Mechanistically, our results suggest that the presence of immune suppressive CD34 1 cells in GM-CSF-producing HNSCC leads to increased tumor recurrence or metastasis. Int. J. Cancer 74:69-74.r 1997 Wiley-Liss, Inc.Head and neck cancers, most of which are squamous cell carcinomas (HNSCC), are vulnerable to immune effector cells such as macrophages, natural killer cells and cytotoxic T-lymphocytes (Chikamatsu et al., 1995;Rabinowich et al., 1992). However, patients with HNSCC cancers are particularly prone to have defects in their immune defenses (Gooding et al., 1995;Hadden et al., 1994). Part of this immune suppression has been shown to be directly induced by soluble immune suppressive factors produced by the cancer (O'Mahony et al., 1993). However, cancers can also mediate immune suppression indirectly by stimulating immune suppressor cell activity. The immune suppressor cells that may be induced by human HNSCC have not been extensively studied or described, but have been well documented in many other cancer types of both humans and animals. Some human cancers induce suppressive T-cells that are inhibitory to immune functions, including anti-tumor T-cell reactivities (Chakraborty et al., 1991). Suppression of T-cell function in patients with HNSCC as well as with other cancers can also be due to monocytes or macrophages secreting the immune suppressive mediator prostaglandin E 2...

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Section: Patient Profile and Data Analysismentioning

confidence: 71%

Section: Human Head and Neck Cancersmentioning

confidence: 99%

Section: Flow Cytometric Analysis Of Intratumoral Cd34 1 Cell Contentmentioning

confidence: 99%

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confidence: 99%

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