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      Tumor-associated macrophages (TAMs): clinical-pathological parameters in squamous cell carcinomas of the lower lip

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          Abstract

          Abstract The objective of this study was to analyze the presence of tumor-associated macrophage (TAM) subpopulations M1 and M2 in squamous cell carcinoma of the lower lip (SCCLL) by immunohistochemitry, and to evaluate the possible role of these subtypes in the development of regional lymph node metastasis and their association with clinical and pathological parameters. Forty-two cases of SCCLL were divided into two groups (21 with and 21 without regional lymph node metastasis). The histopathological grade of malignancy was determined and the material was submitted to double staining with anti-CD68/anti-CD163 and anti-CD68/anti-HLA-DR monoclonal antibodies. The results were analyzed statistically using the Wilcoxon signed-rank and Spearman correlation tests. The M1 and M2 subpopulations were observed in all cases studied. No significant difference was observed between the quantities of M1 and M2 TAMs regarding tumor size (p > 0.05). A significantly larger number of M2 compared to M1 TAMs was observed in tumors without regional lymph node metastasis, tumors in early stages, and low-grade tumors (p < 0.05). No significant difference between the numbers of M1 and M2 TAMs was observed in tumors with regional lymph node metastasis, tumors in advanced stages, and high-grade tumors (p > 0.05). There was a positive weak correlation between M1 and M2 TAMs (r = 0.361; p = 0.019). The results suggest a more important role of M2 TAMs in early stages than advanced stages of lip carcinogenesis. The progression of SCCLL does not seem to be related to an imbalance of macrophage polarization in the microenvironment of these tumors.

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          Most cited references 37

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          The macrophage: past, present and future.

           Siamon Gordon (2007)
          As we approach the centenary of Elie Metchnikoff's Nobel Prize (1908), it is opportune to reflect upon the history of macrophage immunobiology, take stock of current knowledge and anticipate questions for the future. Starting from his appreciation of phagocytosis as an important determinant of host defence against infection and injury, we have learned a great deal about the distribution of macrophages throughout the body, their heterogeneous phenotype and complex functions in tissue homeostasis as well as in innate and acquired immunity. Recent discoveries of Toll-like and other plasma membrane, vacuolar and cytosolic recognition molecules have brought the macrophage and closely related dendritic cells to the centre of immunologic attention, but many earlier discoveries of their cellular and molecular properties have laid a broader foundation to the appreciation of their remarkable plasticity and adaptability to local and systemic cues. Discoveries of pro-inflammatory mediators such as TNF and other secretory products have provided valuable insights into the role of macrophages in many acute and chronic disease processes, and led to the development of effective therapeutics. Much remains to be discovered regarding both their specific functions and by study of their general cellular properties, in vitro and in vivo.
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            Is the invasive front of an oral carcinoma the most important area for prognostication?

             M Bryne (1998)
            The prognosis for patients with oral squamous cell carcinomas is difficult to predict. There is therefore a great need for more reliable prognostic markers which will be of help in the treatment decisions. In this review I present a hypothesis which suggests that molecular and morphological characteristics at the invasive front area of various carcinomas may reflect tumour prognosis better than other parts of the tumour. It is now known that several molecular events of importance for tumour spread like gains and losses of adhesion molecules, secretion of proteolytic enzymes, increased cell proliferation and initiation of angiogenesis occur at the tumour-host interface (invasive front). Consequently, our group has recently developed a simple morphological malignancy grading system that restricts the evaluation to the deep invasive front area of the tumour. Several studies have shown that this system is a significantly better predictor of prognosis than traditionally used morphological systems. All studies performed so far show that invasive front grading is a valuable supplement to clinical staging, suggesting that it should be introduced into the clinic.
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              Role of tumour-associated macrophages in cancer-related inflammation.

              The construction of an inflammatory microenvironment provides the fuel for cancer development and progression. Hence, solid tumors promote infiltration of leukocyte populations, among which tumor-associated macrophages (TAM) represent a paradigm for cancer promoting inflammation. TAM orchestrate various aspects of cancer, including diversion and skewing of adaptive responses, cell growth, angiogenesis, matrix deposition and remodeling, the construction of a metastatic niche and actual metastasis, response to hormones and chemotherapeutic agents. Several evidence indicate that TAM show a remarkable degree of plasticity and functional heterogeneity, suggesting that during tumor progression macrophages undergo a phenotypic 'switch', eventually exhibiting the alternatively activated, 'M2', phenotype, associated with immunosuppression, promotion of tumor angiogenesis and metastasis. While recent studies have attempted to address the role of microenvironment signals on the TAM « reprogramming », the interplay between innate and adaptive immunity is emerging as a crucial step of this event. Here I discuss the evidence for the functional reprogramming of TAM during the course of tumor progression and the molecular mechanisms that regulate such event. Finally, I discuss the implications of this phenomenon for anti-cancer therapies aimed at prompting TAM to mount an effective antitumor response.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Journal
                bor
                Brazilian Oral Research
                Braz. oral res.
                Sociedade Brasileira de Pesquisa Odontológica - SBPqO
                1807-3107
                2016
                : 30
                : 1
                Affiliations
                [1 ] Universidade Estadual da Paraíba Brazil
                [2 ] Universidade Federal de Minas Gerais Brazil
                [3 ] Universidade Federal de Pernambuco Brazil
                Article
                S1806-83242016000100283
                10.1590/1807-3107BOR-2016.vol30.0095

                This work is licensed under a Creative Commons Attribution 4.0 International License.

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                Product Information: website
                Categories
                DENTISTRY, ORAL SURGERY & MEDICINE

                Dentistry

                Immunohistochemistry, Lip, Squamous Cell, Carcinoma

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