Quantification of tumor infiltrating Foxp3+ regulatory T cells enables the identification of high-risk patients for developing synchronous cancers over upper aerodigestive tract

Wang, Wen‐Lun; Chang, Wei‐Lun; Yang, Haw‐Ching; Chang, I‐Wei; Lee, Ching‐Tai; Chang, Chi‐Yang; Lin, Jaw‐Town; Sheu, Bor–Shyang

doi:10.1016/j.oraloncology.2015.04.015

Cited by 28 publications

(27 citation statements)

References 28 publications

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“…42,46 Furthermore, synchronous multifocal cancers, the cancers arising at the same time in different oral cavity area, have more elevated numbers of Treg. 44 This aspect sustains a model where Treg increase is a promoting factor rather than a consequence of cancer development.…”

Section: Treg Significance In Hnscc Prognosissupporting

confidence: 56%

T-helper and T-regulatory cells modulation in head and neck squamous cell carcinoma

Maggioni

Garavello

2017

OncoImmunology

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Head and neck squamous cell carcinoma (HNSCC) is one of the most diffused cancer types, characterized by a high reoccurrence rate, mainly due to the inability of current therapeutic approaches to completely eradicate cancer cells. HNSCC patients often have defective immune functions, thus allowing cancer immune escape and cancer spreading. Particularly important in driving immune escape during HNSCC progression are T-helper and T-regulatory cells. New insights into their mechanisms of action might support the development of effective and long-lasting immunotherapy.

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Section: Treg Significance In Hnscc Prognosissupporting

confidence: 56%

T-helper and T-regulatory cells modulation in head and neck squamous cell carcinoma

Maggioni

Garavello

2017

OncoImmunology

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“…In comparison, lymph vessel invasion and lymph node metastasis were found to be associated with prognosis in the current study. A previous study has shown that an increase in Tregs was associated with CCL22 expression in head and neck SCC . However, the correlation between the expression of CCL22‐positive macrophages, the major source of CCL22, and the prognosis of OSCC is not clear.…”

Section: Discussionmentioning

confidence: 95%

Macrophage CCL22 expression in the tumor microenvironment and implications for survival in patients with squamous cell carcinoma of the tongue

Kimura

Nanbu

Noguchi

et al. 2019

J Oral Pathology Medicine

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Background CCL22, mainly synthesized by monocyte‐derived alternative (M2) macrophages, belongs to the CC family of chemokines. CCR4, the receptor for CCL22, is expressed in regulatory T cells (Tregs) and Th2 cells. The Yamamoto‐Kohama (YK) mode of invasion has been associated with tumor prognosis. Herein, we investigated the role of CCL22 in the tumor microenvironment and its effect on the overall survival rate in patients with tongue squamous cell carcinoma (SCC). Methods Tumor sections obtained from 92 patients with tongue SCC were graded based on the mode of invasion according to the YK classification. The expressions of several markers (CCL22, CD8, and Ki‐67 by immunohistochemistry; CCR4 and FoxP3 by immunofluorescent staining) were evaluated. Student's t test and chi‐square tests were used to compare differences between numerical variables and groups, respectively. Survival curves were plotted according to the Kaplan‐Meier method and compared using a log‐rank test. Hazard ratios and 95% confidence intervals were estimated using univariate or multivariate Cox proportional hazard models. Results The expression of CCL22 was significantly correlated with YK classification, overall survival rate (P < 0.001), a decrease in the number of CD8‐positive cells, and an increase in the tumor Ki‐67 index. In addition, CCR4‐positive cells were observed around CCL22‐positive macrophages. Conclusion These findings indicate that the expression of CCL22 in the tumor microenvironment led to a deterioration in the prognosis of patients with tongue SCC by influencing the balance of M1‐ and M2‐like macrophages.

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“…However, immunotherapeutic approaches are complicated by the profound level of immune suppression in HNSCC patients. This immune suppression is mediate by a variety of cell types including cancer‐associated fibroblasts, regulatory T‐cells (Treg), and myeloid‐derived suppressor cells (MDSC) . Patients with laryngeal squamous cell carcinoma have increased levels of Treg cells and reduced levels of both naïve T‐cells and immune stimulatory Th1 cells .…”

mentioning

confidence: 99%

“…The impact of immune suppressor cells on immune defenses against cancer is supported by studies showing that treatments to reduce levels of MDSC and Treg in HNSCC patients result in T‐cell reactivity against autologous cancer . It has also been shown that an increased level of immune inhibitory cells in HNSCC patients predisposes them to development of synchronous squamous cell carcinomas . Because of the extensive immune dysfunction in HNSCC patients, it may be more realistic to test immune therapeutic approaches in subjects with premalignant lesions that have a high risk at developing HNSCC so as to limit progression of premalignant oral lesions toward HNSCC.…”

mentioning

confidence: 99%

Treatment to sustain a Th17‐type phenotype to prevent skewing toward Treg and to limit premalignant lesion progression to cancer

Young

Levingston

Johnson

2016

Intl Journal of Cancer

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While immune suppression is a hallmark of head and neck squamous cell carcinoma (HSNCC), the immunological impact of premalignant oral lesions, which often precedes development of HNSCC, is unknown. The present study assessed the changes in splenic and draining lymph node CD4+cell populations and their production of select cytokines that occur in mice with carcinogen-induced premalignant oral lesions and the changes that occur as lesions progress to oral cancer. These studies found skewing toward Th1 and Th17-type phenotypes in the spleen and lymph nodes of mice with premalignant oral lesions and a shift to Treg as lesions progress to cancer. Since the role of Th17 cells in the progression from premalignant lesions to cancer is not clear, studies determined the immunological and clinical effect of treating mice bearing premalignant oral lesions with a TGF-β type 1 receptor inhibitor plus IL-23 as an approach to sustain the Th17 phenotype. These studies showed that the treatment approach not only sustained the Th17 phenotype, but also increased distal spleen cell and regional lymph node cell production of other stimulatory/inflammatory mediators and slowed premalignant lesion progression to cancer.

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Quantification of tumor infiltrating Foxp3+ regulatory T cells enables the identification of high-risk patients for developing synchronous cancers over upper aerodigestive tract

Cited by 28 publications

References 28 publications

T-helper and T-regulatory cells modulation in head and neck squamous cell carcinoma

T-helper and T-regulatory cells modulation in head and neck squamous cell carcinoma

Macrophage CCL22 expression in the tumor microenvironment and implications for survival in patients with squamous cell carcinoma of the tongue

Treatment to sustain a Th17‐type phenotype to prevent skewing toward Treg and to limit premalignant lesion progression to cancer

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