Alteration of Macrophage Infiltrating Compartment: A Novel View on Oral Carcinogenesis

Abstract

<b><i>Background:</i></b> The mortality of oral squamous cell carcinoma (OSCC) has remained high for decades; therefore, methods for early detection of OSCC are warranted. However, in the oral cavity, various mucosal diseases may be encountered, including reactive lesions and oral potentially malignant disorders, and it is difficult to differentiate OSCC from these lesions based on both clinical and histopathological findings. It is well known that chronic inflammation contributes to oral cancer development. Macrophages are among the most common inflammatory cells in cancer stromal tissue and have various roles in cancer aggressiveness. Although the roles of macrophages in cancer development have attracted attention, only a few studies have linked macrophages to carcinogenesis, particularly, oral precancerous lesions. <b><i>Summary:</i></b> This review article consists of 3 parts: first, we summarize current knowledge on macrophages in human various epithelial precancerous lesions, excluding the oral cavity, to show the importance and gaps in knowledge regarding macrophages in carcinogenesis; second, we review published data related to the role of macrophages in oral carcinogenesis; finally, we present a novel view on oral carcinogenesis, focusing on crosstalk between epithelial cells and macrophages. <b><i>Key Messages:</i></b> The biological features of macrophages in oral carcinogenesis differ drastically depending on the anatomical compartment that they infiltrate. Focusing on the alteration of macrophage infiltrating compartment may serve as a useful novel approach for studying the role of the macrophages in oral carcinogenesis and for gaining further insight into cancer prevention and early detection.

Microenvironment in Oral Potentially Malignant Disorders: Multi-Dimensional Characteristics and Mechanisms of Carcinogenesis

“…The high expression of the M2 macrophage gene is significantly positively correlated with oral cancer-free survival in 4NQO-treated OPMDs mice. This may be relevant, as the biological features of macrophages in oral carcinogenesis differ drastically depending on the anatomical compartment that they infiltrate [ 38 ]. Meanwhile, macrophages are extremely plastic during macrophage polarization, so they may not be completely either the M1 or M2 type, which affects the OPMDs carcinogenesis in different ways [ 37 ].…”

Tumor Immune Microenvironment Heterogeneity at the Invasion Front and Tumor Center in Oral Squamous Cell Carcinoma as a Perspective of Managing This Cancer Entity

“…Tumor-associated macrophages (TAMs) represent a major component of the OSCC TIME and have a bipolar role, depending on their activation state [ 8 , 9 ]. M1 macrophages are tumor suppressive and facilitate tumor-specific antigen presentation [ 10 ]. In contrast, M2 macrophages (CD163+) are known to reduce radiosensitivity, promote anti-inflammatory response, and play a role in angiogenesis as well as in epithelial-to-mesenchymal transition, a fundamental process of metastasis [ 10 , 11 ].…”

Tongue immune compartment analysis reveals spatial macrophage heterogeneity

“…The characterization of sub-epithelial macrophage subsets is much more enigmatic and so far depended on the histological examination of a few membrane markers 5,6 . For example, human CD163 + macrophages can be found in subepithelial areas of the tongue 6 , a localization that they share with CD11c + "dendritic" cells 7 .…”

“…The characterization of sub-epithelial macrophage subsets is much more enigmatic and so far depended on the histological examination of a few membrane markers 5,6 . For example, human CD163 + macrophages can be found in subepithelial areas of the tongue 6 , a localization that they share with CD11c + "dendritic" cells 7 . Relying on single markers such as CD11c to identify cells of the "dendritic" cell lineage is problematic since various additional cell types, including monocytes, macrophages and lymphocytes, can express CD11c 8 .…”

“…Until now, the characterization of the mononuclear phagocyte compartment of the tongue mainly focused on Langerhans cells that were first described in the mouse epithelium forty years ago 2 and are identified in humans by their exclusive CD1a immunoreactivity 3,4 . The characterization of sub-epithelial macrophage subsets is much more enigmatic and so far depended on the histological examination of a few membrane markers 5,6 . For example, human CD163 + macrophages can be found in subepithelial areas of the tongue 6 , a localization that they share with CD11c + “dendritic” cells 7 .…”