CD163-Positive Macrophages Within the Tumor Stroma Are Associated With Lymphangiogenesis and Lymph Node Metastasis in Oral Squamous Cell Carcinoma

Yamagata, Yuko; Tomioka, Hirofumi; Sakamoto, Kei; Satô, Kiyoshi; Harada, Hiroyuki; Ikeda, Tohru; Kayamori, Kou

doi:10.1016/j.joms.2017.03.009

Cited by 50 publications

(59 citation statements)

References 29 publications

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“…Different types of immune cell are located in the tumour stroma and have key roles in tumour progression. For example, tumour‐associated macrophages have been shown to promote tumour growth and inhibit antitumour immune responses, and their number is positively associated with poor prognosis in OSCC . Inflammatory cells play an important role in cancer progression and predict the prognosis of OSCC .…”

Section: Discussionmentioning

confidence: 99%

Prognostic impact of tumour–stroma ratio in early‐stage oral tongue cancers

et al. 2018

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Section: Discussionmentioning

confidence: 99%

Prognostic impact of tumour–stroma ratio in early‐stage oral tongue cancers

et al. 2018

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“…When Th2 cells accumulate in the periphery of the tumor, the surrounding tumor microenvironment is dominated by Th2 cytokines, such as IL‐4, thereby promoting the differentiation of TAMs into M2‐like macrophages . An increase in this positive mechanism further increases the number of CD163‐positive TAMs surrounding the tumor and promotes lymphatic vessel invasion …”

Section: Discussionmentioning

confidence: 99%

“…Of the several characteristic markers of macrophages, CD163 has been reported as a highly specialized marker of M2 monocyte‐derived alternative macrophages . Furthermore, CD163‐positive TAMs are chiefly associated with lymphatic vessel invasion and lymph node metastasis in OSCC via VEGF‐C expression …”

Section: Introductionmentioning

confidence: 99%

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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“…In primary OSCC, high macrophage numbers have been linked to poor prognosis and increased lymph node metastasis . However, there is some disagreement as to whether macrophage densities in the tumour, invasive edge or stroma are significant and whether this association is only found when staining for M2 macrophage markers.…”

Section: The Tumour Microenvironment In Enementioning

confidence: 99%

Extranodal extension in oral cancer: A role for the nodal microenvironment?

Pilborough

Lambert

Khurram

2019

J Oral Pathology Medicine

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Oral squamous cell carcinoma (OSCC) is a significant cause of morbidity and mortality worldwide and accounts for the majority of head and neck cancers. Metastasis of primary tumours, primarily to cervical lymph nodes in the neck, is associated with worsening prognosis. Furthermore, the prognosis of patients with extranodal extension of metastatic tumour from the lymph nodes into the neck tissues is particularly poor. The factors affecting this process are poorly understood, and detection is difficult pre‐surgery. Mounting evidence shows that components of the tumour microenvironment including cancer‐associated fibroblasts, vascular and lymphatic endothelial cells, the extracellular matrix and inflammatory immune cells, are important modulators of tumour behaviour in primary OSCC and other cancers. However, little is known about the lymph node microenvironment, its response to tumour presence and role in extranodal extension. In addition, there are many lymph node‐specific cell types and structures, such as fibroblast reticular cells and high endothelial venules, making the lymph node microenvironment distinct from that found at primary tumour sites, and which contribute to the nodal response to tumour presence. This review details the current knowledge regarding the lymph node tumour microenvironment in OSCC and its role in lymph node metastasis and extranodal extension and relates this to features of the primary tumour. Understanding the role that the lymph node microenvironment plays in promoting tumour development and extranodal extension may aid the identification of novel biomarkers and alternative treatment strategies to improve the prognosis of patients with advanced OSCC.

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CD163-Positive Macrophages Within the Tumor Stroma Are Associated With Lymphangiogenesis and Lymph Node Metastasis in Oral Squamous Cell Carcinoma

Cited by 50 publications

References 29 publications

Prognostic impact of tumour–stroma ratio in early‐stage oral tongue cancers

Prognostic impact of tumour–stroma ratio in early‐stage oral tongue cancers

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

Extranodal extension in oral cancer: A role for the nodal microenvironment?

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