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CD45RA-Foxp3high but not CD45RA+Foxp3low suppressive T regulatory cells increased in the peripheral circulation of patients with head and neck squamous cell carcinoma and correlated with tumor progression.

Sun W, Li WJ, Wu CY, Zhong H, Wen WP - J. Exp. Clin. Cancer Res. (2014)

Bottom Line: However, the frequency of Tregs was similar between patients with oral cavity squamous cell carcinoma and healthy donors (P = 0.269).Functionally study revealed that CD45RA-CD25+++ Tregs significantly inhibit the proliferation of CD4+CD25- T cells (P < 0.001) and secrete lower levels of cytokines (P < 0.01) compared with CD45RA-CD25++CD4+ T cells.Importantly, the frequency of CD45RA-Foxp3high Tregs positively correlate with tumor stage (P < 0.0001) and nodal status (P < 0.0001).

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Otorhinolaryngology Head and Neck Surgery, the First Affiliated Hospital of Sun Yat-sen University, 2nd Zhongshan Road 58#, Guangzhou 510080, Guangdong, P,R, China. wenwp@mail.sysu.edu.cn.

ABSTRACT

Background: T regulatory cells (Tregs) contribute to the progression of head and neck squamous cell carcinoma (HNSCC) by suppressing antitumor immunity. However, little is known regarding the functional heterogeneity of Tregs in HNSCC patients.

Methods: Using multicolor flow cytometry, the frequency of three Treg subsets, separated on the basis of CD45RA and Foxp3, from the peripheral circulation of newly-presenting HNSCC patients (19 oral cavity squamous cell carcinoma, 20 hypopharyngeal squamous cell carcinoma, 18 nasopharyngeal squamous cell carcinoma, 19 oropharyngeal squamous cell carcinoma, and 36 laryngeal squamous cell carcinoma) were assessed with regard to 31 healthy donors and clinicopathological features. Moreover, the functional capacity of each Treg subsets was evaluated based on CD45RA and CD25 expression.

Results: The frequency of Tregs in the peripheral circulation of HNSCC patients as a whole cohort was higher than in healthy donors (P < 0.0001). However, the frequency of Tregs was similar between patients with oral cavity squamous cell carcinoma and healthy donors (P = 0.269). Further dividing Tregs into three subsets based on Foxp3 and CD45RA expression revealed that the frequency of CD45RA-Foxp3high Tregs and CD45RA-Foxp3lowCD4+ T cells in patients with HNSCC developing from different subsites was higher than in healthy donors (P < 0.0001, P < 0.0001), whereas the frequency of CD45RA+Foxp3low Tregs was lower than in healthy donors (P < 0.0001). Functionally study revealed that CD45RA-CD25+++ Tregs significantly inhibit the proliferation of CD4+CD25- T cells (P < 0.001) and secrete lower levels of cytokines (P < 0.01) compared with CD45RA-CD25++CD4+ T cells. Importantly, the frequency of CD45RA-Foxp3high Tregs positively correlate with tumor stage (P < 0.0001) and nodal status (P < 0.0001).

Conclusions: CD45RA-Foxp3high Tregs increase in the peripheral circulation of HNSCC patients, and correlate with tumor stage and nodal status; suggesting a role in tumor progression which may be manipulated by future immunotherapy.

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Percentage of Treg subsets in HNSCC patient subgroups. (A) Flow dot plots of Tregs (Foxp3low and Foxp3high Tregs) (top) and each Treg subset (I: CD45RA+Foxp3low Tregs; II: CD45RA-Foxp3high Tregs; III: CD45RA-Foxp3lowCD4+ T cells) (bottom) for one representative HD and patients with HPSCC, NPSCC, OPSCC, and LSCC. (B) Percentage (means ± SD) of Tregs and each Treg subset in HNSCC patient subgroups or HD. (C) Different proportions (means) of each Treg subset in HNSCC patient subgroups are presented. HD: healthy donors. OCSCC: oral squamous cell carcinoma. HPSCC: hypopharyngeal squamous cell carcinoma. NPSCC: nasopharyngeal squamous cell carcinoma. OPSCC: oropharyngeal squamous cell carcinoma. LSCC: laryngeal squanmous cell carcinoma. Statistical comparisons were performed using the Kruskal–Wallis test.
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Figure 4: Percentage of Treg subsets in HNSCC patient subgroups. (A) Flow dot plots of Tregs (Foxp3low and Foxp3high Tregs) (top) and each Treg subset (I: CD45RA+Foxp3low Tregs; II: CD45RA-Foxp3high Tregs; III: CD45RA-Foxp3lowCD4+ T cells) (bottom) for one representative HD and patients with HPSCC, NPSCC, OPSCC, and LSCC. (B) Percentage (means ± SD) of Tregs and each Treg subset in HNSCC patient subgroups or HD. (C) Different proportions (means) of each Treg subset in HNSCC patient subgroups are presented. HD: healthy donors. OCSCC: oral squamous cell carcinoma. HPSCC: hypopharyngeal squamous cell carcinoma. NPSCC: nasopharyngeal squamous cell carcinoma. OPSCC: oropharyngeal squamous cell carcinoma. LSCC: laryngeal squanmous cell carcinoma. Statistical comparisons were performed using the Kruskal–Wallis test.

Mentions: The frequency of CD45RA-Foxp3lowCD4+ T cells in patients with OPSCC (5.86 ± 1.26%, P < 0.0001), LSCC (5.10 ± 1.14%, P < 0.0001), HPSCC (6.63 ± 1.67%, P < 0.0001), and NPSCC (5.37 ± 1.66%, P = 0.002) were higher than in HD (3.70 ± 1.58%). However, the frequency of CD45RA-Foxp3lowCD4+ T cells was similar between OCSCC patients (4.24 ± 1.31%) and HD (3.70 ± 1.58%) (P = 0.093) (Figure 4A-C).


CD45RA-Foxp3high but not CD45RA+Foxp3low suppressive T regulatory cells increased in the peripheral circulation of patients with head and neck squamous cell carcinoma and correlated with tumor progression.

Sun W, Li WJ, Wu CY, Zhong H, Wen WP - J. Exp. Clin. Cancer Res. (2014)

Percentage of Treg subsets in HNSCC patient subgroups. (A) Flow dot plots of Tregs (Foxp3low and Foxp3high Tregs) (top) and each Treg subset (I: CD45RA+Foxp3low Tregs; II: CD45RA-Foxp3high Tregs; III: CD45RA-Foxp3lowCD4+ T cells) (bottom) for one representative HD and patients with HPSCC, NPSCC, OPSCC, and LSCC. (B) Percentage (means ± SD) of Tregs and each Treg subset in HNSCC patient subgroups or HD. (C) Different proportions (means) of each Treg subset in HNSCC patient subgroups are presented. HD: healthy donors. OCSCC: oral squamous cell carcinoma. HPSCC: hypopharyngeal squamous cell carcinoma. NPSCC: nasopharyngeal squamous cell carcinoma. OPSCC: oropharyngeal squamous cell carcinoma. LSCC: laryngeal squanmous cell carcinoma. Statistical comparisons were performed using the Kruskal–Wallis test.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4022051&req=5

Figure 4: Percentage of Treg subsets in HNSCC patient subgroups. (A) Flow dot plots of Tregs (Foxp3low and Foxp3high Tregs) (top) and each Treg subset (I: CD45RA+Foxp3low Tregs; II: CD45RA-Foxp3high Tregs; III: CD45RA-Foxp3lowCD4+ T cells) (bottom) for one representative HD and patients with HPSCC, NPSCC, OPSCC, and LSCC. (B) Percentage (means ± SD) of Tregs and each Treg subset in HNSCC patient subgroups or HD. (C) Different proportions (means) of each Treg subset in HNSCC patient subgroups are presented. HD: healthy donors. OCSCC: oral squamous cell carcinoma. HPSCC: hypopharyngeal squamous cell carcinoma. NPSCC: nasopharyngeal squamous cell carcinoma. OPSCC: oropharyngeal squamous cell carcinoma. LSCC: laryngeal squanmous cell carcinoma. Statistical comparisons were performed using the Kruskal–Wallis test.
Mentions: The frequency of CD45RA-Foxp3lowCD4+ T cells in patients with OPSCC (5.86 ± 1.26%, P < 0.0001), LSCC (5.10 ± 1.14%, P < 0.0001), HPSCC (6.63 ± 1.67%, P < 0.0001), and NPSCC (5.37 ± 1.66%, P = 0.002) were higher than in HD (3.70 ± 1.58%). However, the frequency of CD45RA-Foxp3lowCD4+ T cells was similar between OCSCC patients (4.24 ± 1.31%) and HD (3.70 ± 1.58%) (P = 0.093) (Figure 4A-C).

Bottom Line: However, the frequency of Tregs was similar between patients with oral cavity squamous cell carcinoma and healthy donors (P = 0.269).Functionally study revealed that CD45RA-CD25+++ Tregs significantly inhibit the proliferation of CD4+CD25- T cells (P < 0.001) and secrete lower levels of cytokines (P < 0.01) compared with CD45RA-CD25++CD4+ T cells.Importantly, the frequency of CD45RA-Foxp3high Tregs positively correlate with tumor stage (P < 0.0001) and nodal status (P < 0.0001).

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Otorhinolaryngology Head and Neck Surgery, the First Affiliated Hospital of Sun Yat-sen University, 2nd Zhongshan Road 58#, Guangzhou 510080, Guangdong, P,R, China. wenwp@mail.sysu.edu.cn.

ABSTRACT

Background: T regulatory cells (Tregs) contribute to the progression of head and neck squamous cell carcinoma (HNSCC) by suppressing antitumor immunity. However, little is known regarding the functional heterogeneity of Tregs in HNSCC patients.

Methods: Using multicolor flow cytometry, the frequency of three Treg subsets, separated on the basis of CD45RA and Foxp3, from the peripheral circulation of newly-presenting HNSCC patients (19 oral cavity squamous cell carcinoma, 20 hypopharyngeal squamous cell carcinoma, 18 nasopharyngeal squamous cell carcinoma, 19 oropharyngeal squamous cell carcinoma, and 36 laryngeal squamous cell carcinoma) were assessed with regard to 31 healthy donors and clinicopathological features. Moreover, the functional capacity of each Treg subsets was evaluated based on CD45RA and CD25 expression.

Results: The frequency of Tregs in the peripheral circulation of HNSCC patients as a whole cohort was higher than in healthy donors (P < 0.0001). However, the frequency of Tregs was similar between patients with oral cavity squamous cell carcinoma and healthy donors (P = 0.269). Further dividing Tregs into three subsets based on Foxp3 and CD45RA expression revealed that the frequency of CD45RA-Foxp3high Tregs and CD45RA-Foxp3lowCD4+ T cells in patients with HNSCC developing from different subsites was higher than in healthy donors (P < 0.0001, P < 0.0001), whereas the frequency of CD45RA+Foxp3low Tregs was lower than in healthy donors (P < 0.0001). Functionally study revealed that CD45RA-CD25+++ Tregs significantly inhibit the proliferation of CD4+CD25- T cells (P < 0.001) and secrete lower levels of cytokines (P < 0.01) compared with CD45RA-CD25++CD4+ T cells. Importantly, the frequency of CD45RA-Foxp3high Tregs positively correlate with tumor stage (P < 0.0001) and nodal status (P < 0.0001).

Conclusions: CD45RA-Foxp3high Tregs increase in the peripheral circulation of HNSCC patients, and correlate with tumor stage and nodal status; suggesting a role in tumor progression which may be manipulated by future immunotherapy.

Show MeSH
Related in: MedlinePlus