Clinicopathological significance of chemokine receptor (<scp>CCR</scp>1, <scp>CCR</scp>3, <scp>CCR</scp>4, <scp>CCR</scp>5, <scp>CCR</scp>7 and <scp>CXCR</scp>4) expression in head and neck squamous cell carcinomas

González‐Arriagada, Wilfredo Alejandro; Lozano-Burgos, Carlos; Zúñiga-Moreta, Rodrigo; González-Díaz, Paulina; Coletta, Ricardo D.

doi:10.1111/jop.12736

Cited by 49 publications

(39 citation statements)

References 29 publications

(46 reference statements)

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“…3 Overexpressed CXCR4 is predominantly associated with progression and poor prognosis in several tumors including oral cancer. 4,5 We previously proved that blockade of CXCR4/SDF-1 axis by reducing the secretion of SDF-1 derived from cancer-associated fibroblasts could significantly suppress the proliferation, invasion and migration of cancer cells in vitro, 6 similar results were observed under suppression of CXCR4 activity either by shRNA or pharmacological inhibitor. 7,8 Increasing evidences show that CXCR4 participates in chemotherapy resistance in various cancers such as breast cancer, ovarian cancer, and nonsmall cell lung cancer.…”

Section: Introductionmentioning

confidence: 76%

CXCR4 enhances cisplatin resistance of human tongue squamous cell carcinoma

Zhuang

Zhou

2018

J Oral Pathology Medicine

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Background The chemokine receptor 4 (CXCR4) plays an important role in tumor progression. Overexpressed CXCR4 is associated with a poor prognosis of patient with head and neck squamous cell carcinomas. However, the correlation between CXCR4 and chemotherapy resistance in tongue squamous cell carcinoma (TSCC) remains obscure. Methods Stable cisplatin‐resistant CAL27 CDDP and SCC25 CDDP cells were established and identified by CCK8 assay, and the CXCR4 expression was detected using qRT‐PCR and Western blot. CXCR4‐siRNA was transfected into TSCC CDDP cells, whose transfect efficiency was examined. Cisplatin sensitivity was further detected, as well as several proliferation and apoptosis‐related proteins. Results CAL27 CDDP and SCC25 CDDP cells were successfully established, which exhibited significantly higher cell viability and less apoptosis under cisplatin stimulation than that of parental cells. CXCR4 expression was increased in TSCC CDDP cells. After transfection of CXCR4‐siRNA, the expression of CXCR4 was reduced by 73% and 78% in CAL27 CDDP and SCC25 CDDP cells, respectively. CCK8 assay and flow cytometry assay revealed that the proliferative capacity under cisplatin stimulation significantly decreased after CXCR4 silencing. Moreover, increased TSCC CDDP cells were arrested in the G0/G1 phase after knockdown of CXCR4. Compared with negative control group, the expression of cyclin D1 and p‐AKT decreased, while that of p‐caspase‐3 and Bax significantly increased. Conclusions Silencing CXCR4 may evidently inhibit proliferation, induce apoptosis and enhance cisplatin sensitivity of TSCC CDDP cells by reduced cyclin D1 and p‐AKT, and increased p‐caspase‐3 and Bax.

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Section: Introductionmentioning

confidence: 76%

CXCR4 enhances cisplatin resistance of human tongue squamous cell carcinoma

Zhuang

Zhou

2018

J Oral Pathology Medicine

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“…CCR4 has been proven that it may have an important role in HNSCC progression, regional lymph node metastasis and recurrence. Signi cant progress has been made on the correlation of overall survival with gene expression in HNSCCs (19)(20)(21). Many of these experiments were done in tumor cell lines, animal models, or patients' tumor samples.…”

Section: Discussionmentioning

confidence: 99%

Mining TCGA database for prognostic genes in head and neck squamous cell carcinoma microenvironment

Ran

Long

Yan

et al. 2019

Preprint

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Background Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignant tumors. Many previous reports have already shown that the extent of infiltrating immune and stromal cells in tumor tissues and the tumor microenvironment (TME) cells play a significant role in the overall prognosis. Methods The convenient access to The Cancer Genome Atlas (TCGA) database facilitates global gene expression profiling and database mining in a large‐scale for potential correlation between genes and overall survival of a variety of malignancies including HNSCC. The quantification of the immune and stromal components in tumor tissues could be facilitated by calculating mmune scores and stromal scores on the basis of Estimation of stromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) algorithm could facilitate the quantification of the immune and stromal components in tumor tissues. The effects of genes involved in immune and stromal cells on prognosis were categorized. Prognosis associated genes of HNSCC patients were further identified. Result This study showed that GIMAP6, SELL, TIFAB, KCNA3, P2RY8 and CCR4 may mediate immune response, extracellular matrix, and immunoglobulin binding via neutrophil activation in HNSCC. Conclusion Depicting a comprehensive landscape of the TME characteristics of HNSCC may therefore help to interpret the responses of HNSCC to immunotherapies and provide new strategies for the treatment of cancers.

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“…The increased expression of CCR7 on tumor cells has been shown to be associated with a poor prognosis and with the development of lymph node metastases in HNSCC [11,42]. While the expression of CCR7 on HNSCC cells is increased, both in cell lines and patients [10], the frequency of peripheral CD8 + CCR7 + T c cells has been found to be decreased in HNSCC patients [12,13], which in turn is associated with disease recurrence.…”

Section: Expression Of Chemokine Receptor Ccr7mentioning

confidence: 99%

Age-related changes in T lymphocytes of patients with head and neck squamous cell carcinoma

et al. 2020

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Introduction: The number of aging cancer patients has increased continuously and will do so further in the future. The immune system of elderly people experiences critical changes over the time. Therefore, tumor-induced changes in the immune system are believed to differ in young and elderly cancer patients as well. Methods: The effect of aging on the immune system was measured in peripheral blood lymphocytes (PBL) of healthy volunteers (n = 48, 21-84 yrs.) divided into three different age groups. Seventy years was set as a cutoff for defining subjects as elderly. Results were compared to two groups of adult cancer patients, which donated PBL and tumor infiltrating lymphocytes (TIL): young cancer patients (40-69 yrs.; blood: n = 13; TIL: n = 17) and elderly cancer patients (70-90 yrs.; blood: n = 20; TIL: n = 15) with head and neck squamous cell carcinoma (HNSCC). Frequencies and phenotypes of CD4 + and CD8 + T cells as well as regulatory T cells (T reg) were assessed by flow cytometry. Results: We observed lower frequencies of CD8 + cytotoxic T cells during aging in both groups. Frequencies of tumor infiltrating regulatory T cells were significantly higher than in the peripheral blood but showed a significant decline in older tumor patients. With increasing age, expression of immunosuppressive CD73 and CCR7 was lower and expression of PD1 elevated on peripheral T cells in healthy volunteers and tumor patients. Conclusion: Immunosenescence takes place in healthy donors and cancer patients. Our results suggest that in elderly tumor patients, the immune system is impaired and the tumor-induced immune escape is less pronounced. The increased expression of PD1 implies the potential for effective immunotherapies in elderly, as treatment with checkpoint inhibitors could be more beneficial for elderly HNSCC patients.

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Clinicopathological significance of chemokine receptor (CCR1, CCR3, CCR4, CCR5, CCR7 and CXCR4) expression in head and neck squamous cell carcinomas

Abstract: These findings show that chemokine receptors may have an important role in head and neck squamous cell carcinoma progression, regional lymph node metastasis and recurrence.

Cited by 49 publications

References 29 publications

CXCR4 enhances cisplatin resistance of human tongue squamous cell carcinoma

CXCR4 enhances cisplatin resistance of human tongue squamous cell carcinoma

Mining TCGA database for prognostic genes in head and neck squamous cell carcinoma microenvironment

Age-related changes in T lymphocytes of patients with head and neck squamous cell carcinoma

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