Myeloid-derived Suppressor Cells (MDSCs) in OSCC Patients

NCT ID: NCT04387682

Last Updated: 2020-05-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

130 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-03-22

Study Completion Date

2021-03-21

Brief Summary

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Oral squamous cell carcinoma (OSCC) has the highest annual increase in the rate of death among the top 10 leading cancers in Taiwan. This research aimed to explore whether increased anti-tumor immunity for OSCCs reduces the recurrence rate or improves survival. We first identified CD33+/CD11b+/HLA-DR-/low/CD14+/- as myeloid-derived suppressor cell (MDSC) surface markers by using flow cytometry to compare the MDSC frequency of OSCCs with blood samples from healthy donors (HDs). We then re-confirmed the suppression of T cell proliferation and function achieved by co-culturing with OSCC-educated MDSCs. We subsequently explore whether using particulate β-glucan as a food-grade supplement promotes the human immune system via subversion of immune modulatory MDSCs. Lastly, we correlated clinicopathological parameters with MDSCs and β-glucan administration to examine anti-tumor immunity, and to predict the therapeutic effect and prognosis in OSCC patients..

Detailed Description

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Oral squamous cell carcinoma (OSCC) has the highest annual increase in the rate of death among the top 10 leading cancers in Taiwan. This research aimed to explore whether increased anti-tumor immunity for OSCCs reduces the recurrence rate or improves survival. We first identified CD33+/CD11b+/HLA-DR-/low/CD14+/- as myeloid-derived suppressor cell (MDSC) surface markers by using flow cytometry to compare the MDSC frequency of OSCCs with blood samples from healthy donors (HDs). We then re-confirmed the suppression of T cell proliferation and function achieved by co-culturing with OSCC-educated MDSCs.

Clinically, we enrolled 100 OSCC patients and 30 HDs to demonstrate a significantly higher MDSC frequency in OSCC candidates than HDs. To determine whether using β-glucan as a food-grade supplement promotes the immune system of OSCC patients, we further allocated OSCC patients with and without pre-surgical administration of whole glucan particle β-glucan to groups II and III, respectively (with group I being the HDs).

We will explore whether using particulate β-glucan as a food-grade supplement promotes the human immune system via subversion of immune modulatory MDSCs. Lastly, we correlated clinicopathological parameters with MDSCs and β-glucan administration to examine anti-tumor immunity, and to predict the therapeutic effect and prognosis in OSCC patients.

Conditions

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Squamous Cell Carcinoma of the Oral Cavity

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Oral squamous cell carcinoma (OSCC) subject and healthy donors (HDs) subject
Primary Study Purpose

PREVENTION

Blinding Strategy

SINGLE

Participants

Study Groups

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OSCC subjects with β-glucan supplement

Oral squamous cell carcinoma subjects with pre-surgical administration of whole glucan particle β-glucan

Group Type OTHER

β-glucan

Intervention Type DIETARY_SUPPLEMENT

β-glucan, a biological response regulator, derived from yeast has been known for more than 45 years, and has anti-infective and anti-tumor activities. β-glucan is a molecule with a β-1,3-linked D-glucose backbone and β-1,6-linked side chains. Thus far, at least 4 receptors for β-glucan have been discovered in humans, which are surface antigens associated with macrophages or myeloid precursor cells as complement receptor 3 (CR3; CD11b/CD18, Mac-1, αMβ2 integrin) (Vetvicka et al. 1996; Xia et al. 1999), lactosylceramide (Zimmerman et al. 1998), scavenger receptor (Rice et al. 2002) and dectin-1 (Brown et al. 2003; Taylor et al. 2007; Saijo et al. 2007).

Healthy donors

healthy donors without pre-surgical administration of whole glucan particle β-glucan

Group Type NO_INTERVENTION

No interventions assigned to this group

OSCC subjects without β-glucan supplement

Oral squamous cell carcinoma subjects without pre-surgical administration of whole glucan particle β-glucan

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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β-glucan

β-glucan, a biological response regulator, derived from yeast has been known for more than 45 years, and has anti-infective and anti-tumor activities. β-glucan is a molecule with a β-1,3-linked D-glucose backbone and β-1,6-linked side chains. Thus far, at least 4 receptors for β-glucan have been discovered in humans, which are surface antigens associated with macrophages or myeloid precursor cells as complement receptor 3 (CR3; CD11b/CD18, Mac-1, αMβ2 integrin) (Vetvicka et al. 1996; Xia et al. 1999), lactosylceramide (Zimmerman et al. 1998), scavenger receptor (Rice et al. 2002) and dectin-1 (Brown et al. 2003; Taylor et al. 2007; Saijo et al. 2007).

Intervention Type DIETARY_SUPPLEMENT

Eligibility Criteria

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Inclusion Criteria

* Oral squamous cell carcinoma (OSCC) subjects without other cancer diagnosis
* healthy donors (HDs)

Exclusion Criteria

* pregnant woman
Minimum Eligible Age

20 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Taiwan University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Shih-Jung Cheng, DDS, PhD

Role: PRINCIPAL_INVESTIGATOR

National Taiwan University Hospital

Locations

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National Taiwan University Hospital

Taipei, , Taiwan

Site Status

Countries

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Taiwan

References

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Albeituni SH, Ding C, Liu M, Hu X, Luo F, Kloecker G, Bousamra M 2nd, Zhang HG, Yan J. Correction: Yeast-Derived Particulate beta-Glucan Treatment Subverts the Suppression of Myeloid-Derived Suppressor Cells (MDSC) by Inducing Polymorphonuclear MDSC Apoptosis and Monocytic MDSC Differentiation to APC in Cancer. J Immunol. 2016 May 1;196(9):3967. doi: 10.4049/jimmunol.1600346. No abstract available.

Reference Type RESULT
PMID: 27183652 (View on PubMed)

Allendorf DJ, Yan J, Ross GD, Hansen RD, Baran JT, Subbarao K, Wang L, Haribabu B. C5a-mediated leukotriene B4-amplified neutrophil chemotaxis is essential in tumor immunotherapy facilitated by anti-tumor monoclonal antibody and beta-glucan. J Immunol. 2005 Jun 1;174(11):7050-6. doi: 10.4049/jimmunol.174.11.7050.

Reference Type RESULT
PMID: 15905548 (View on PubMed)

Brown GD, Herre J, Williams DL, Willment JA, Marshall AS, Gordon S. Dectin-1 mediates the biological effects of beta-glucans. J Exp Med. 2003 May 5;197(9):1119-24. doi: 10.1084/jem.20021890. Epub 2003 Apr 28.

Reference Type RESULT
PMID: 12719478 (View on PubMed)

Chen WC, Lai CH, Chuang HC, Lin PY, Chen MF. Inflammation-induced myeloid-derived suppressor cells associated with squamous cell carcinoma of the head and neck. Head Neck. 2017 Feb;39(2):347-355. doi: 10.1002/hed.24595. Epub 2016 Oct 3.

Reference Type RESULT
PMID: 27696591 (View on PubMed)

Gabrilovich DI, Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol. 2009 Mar;9(3):162-74. doi: 10.1038/nri2506.

Reference Type RESULT
PMID: 19197294 (View on PubMed)

Gabrilovich DI, Ostrand-Rosenberg S, Bronte V. Coordinated regulation of myeloid cells by tumours. Nat Rev Immunol. 2012 Mar 22;12(4):253-68. doi: 10.1038/nri3175.

Reference Type RESULT
PMID: 22437938 (View on PubMed)

Other Identifiers

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201701065RIPB

Identifier Type: -

Identifier Source: org_study_id

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