Myeloid-derived Suppressor Cells (MDSCs) in OSCC Patients

Squamous Cell Carcinoma of the Oral Cavity Clinical Trial

Official title:

Myeloid-derived Suppressor Cells (MDSCs) Detection Before and After Beta-glucan Administration in Oral Squamous Cell Carcinoma Patients

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04387682
• Other study ID #: 201701065RIPB
• Status: Active, not recruiting
• Phase: N/A
• Start date: March 22, 2017
• Est. completion date: March 21, 2021

Study information

• Verified date: April 2020
• Source: National Taiwan University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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..

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 130
• Est. completion date: March 21, 2021
• Est. primary completion date: December 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 80 Years

Eligibility

Inclusion Criteria:

• Oral squamous cell carcinoma (OSCC) subjects without other cancer diagnosis

• healthy donors (HDs)

Exclusion Criteria:

• pregnant woman

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Squamous Cell Carcinoma of the Oral Cavity

Intervention

Dietary Supplement:
• ß-glucan
ß-glucan, a biological response regulator, derived from yeast has been known for more than 45 years, and has anti-infective and anti-tumor activities. ß-glucan is a molecule with a ß-1,3-linked D-glucose backbone and ß-1,6-linked side chains. Thus far, at least 4 receptors for ß-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, aMß2 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).

Locations

Country	Name	City	State
Taiwan	National Taiwan University Hospital	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
National Taiwan University Hospital

Country where clinical trial is conducted

Taiwan, 

References & Publications (6)

Albeituni SH, Ding C, Liu M, Hu X, Luo F, Kloecker G, Bousamra M 2nd, Zhang HG, Yan J. Correction: Yeast-Derived Particulate ß-Glucan Treatment Subverts the Suppression of Myeloid-Derived Suppressor Cells (MDSC) by Inducing Polymorphonuclear MDSC Apoptosi — View Citation

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. 20 — View Citation

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. Epub 2003 Apr 28. — View Citation

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. — View Citation

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. Review. — View Citation

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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	recurrence-free survival rate or overall survival rate	This research aimed to explore whether particulate ß-glucan as a crucial preoperative adjuvant increasing anti-tumor immunity for OSCCs reduces the recurrence rate or improves survival. Clinically, we enrolled 100 OSCC patients and 30 HDs, and further allocated OSCC patients with and without pre-surgical administration of whole glucan particle ß-glucan to groups II and III, respectively (with group I being the HDs). we correlated clinicopathological parameters with MDSCs and ß-glucan administration to examine anti-tumor immunity, and to evaluate recurrence-free survival rate or overall survival rate in OSCC patients.	2 years