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

Lúcio, Priscilla Suassuna Carneiro; Ribeiro, Daniela Cotta; Aguiar, Maria Cássia Ferreira de; Alves, Pollianna Muniz; Nonaka, Cassiano Francisco Weege; Godoy, Gustavo Pina

doi:10.1590/1807-3107bor-2016.vol30.0095

Cited by 8 publications

(8 citation statements)

References 36 publications

(59 reference statements)

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“…In some studies, 10 "hot" fields were chosen to quantify TAMs before obtaining an average, while others settled with three or five "hot" fields. As for counting TAMs, certain papers applied software such as ImageScope and ImageJ Cell, while others consulted two pathologists with vast experience to quantify TAMs manually (23,39,69,70,75).…”

Section: Quantification Of Tumor-associated Macrophagesmentioning

confidence: 99%

Evaluating the Polarization of Tumor-Associated Macrophages Into M1 and M2 Phenotypes in Human Cancer Tissue: Technicalities and Challenges in Routine Clinical Practice

et al. 2020

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Tumor-associated macrophages (TAMs) as immune cells within the tumor microenvironment have gained much interests as basic science regarding their roles in tumor progression unfolds. Better understanding of their polarization into pro-tumoral phenotype to promote tumor growth, tumor angiogenesis, immune evasion, and tumor metastasis has prompted various studies to investigate their clinical significance as a biomarker of predictive and prognostic value across different cancer types. Yet, the methodologies to investigate the polarization phenomena in solid tumor tissue vary. Nonetheless, quantifying the ratio of M1 to M2 TAMs has emerged to be a prevailing parameter to evaluate this polarization phenomena for clinical application. This mini-review focuses on recent studies exploring clinical significance of M1/M2 TAM ratio in human cancer tissue and critically evaluates the technicalities and challenges in quantifying this parameter for routine clinical practice. Immunohistochemistry appears to be the preferred methodology for M1/M2 TAM evaluation as it is readily available in clinical laboratories, albeit with certain limitations. Recommendations are made to standardize the quantification of TAMs for better transition into clinical practice and for better comparison among studies in various populations of patients and cancer types.

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Section: Quantification Of Tumor-associated Macrophagesmentioning

confidence: 99%

Evaluating the Polarization of Tumor-Associated Macrophages Into M1 and M2 Phenotypes in Human Cancer Tissue: Technicalities and Challenges in Routine Clinical Practice

et al. 2020

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“…HLA-DR immunoexpression was evaluated quantitatively using an adaptation of the method proposed by Lúcio et al 20 At 100× magnification, the fields (5 for AC and 10 for LLSCC) containing the largest number of immunostained cells were identified. At 400× magnification, digital images of these microscopic fields were acquired with a Leica ICC 50HD camera (Leica Microsystems Vertrieb GmbH, Wetzlar, Germany) and transferred to the ImageJ® program (National Institute of Mental Health, Bethesda, USA).…”

Section: Immunohistochemical Analysismentioning

confidence: 99%

Immunoexpression of human leukocyte antigen-DR in actinic cheilitis and lower lip squamous cell carcinoma

et al. 2019

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The aim of this study was to evaluate the immunoexpression of human leukocyte antigen-DR (HLA-DR) in actinic cheilitis (AC) and lower lip squamous cell carcinoma (LLSCC), and to correlate the findings with clinical (tumor size/extent, regional lymph node metastasis, and clinical stage) and histopathological (grade of epithelial dysplasia and inflammatory infiltrate for AC and histopathological grade of malignancy for LLSCC) parameters. Twenty-four AC and 48 LLSCC cases (24 with regional nodal metastasis and 24 without regional nodal metastasis) were selected. The scores of immunopositive cells for HLA-DR in the epithelial component of the lesions were assessed and the results were analyzed statistically using the nonparametric Mann-Whitney test. Epithelial expression of HLA-DR was observed in only five (20.8%) cases of AC (two low-grade and three high-grade lesions), with a very low median score of immunopositivity. By contrast, expression of HLA-DR was found in most LLSCC (97.9%), with a relatively high median score of positive cells. The score of HLA-DR-positive cells tended to be higher in tumors with regional lymph node metastasis, tumors in advanced clinical stages, and low-grade tumors, but the difference was not statistically significant (p > 0.05). In addition, there was a tendency towards higher expression of HLA-DR in highly/moderately keratinized tumors, and tumors with little/moderate nuclear pleomorphism (p > 0.05). The results suggest a potential role of HLA-DR in lip carcinogenesis, particularly in the development and progression of LLSCC. The expression of this protein can be related to the degree of cell differentiation in these tumors.

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“…A frequência de MATs tem sido associados com o grau de diferenciação celular (Bôas et al, 2013), estadiamento clínico (Marcus et al, 2004;Weber et al, 2016) e sobrevida (Liu et al, 2008;Balermpas et al, 2014;Hu et al, 2016), dentro (2015), avaliando a importância da localização de macrófagos CD68+ em diferentes localizações, não observaram diferenças significantes quanto a expressão de células CD68+ no estroma e nos ninhos tumorais em pacientes com menos de 55 anos e acima de 55 anos (Ni et al, 2015). (Lucio et al, 2016). Wei e Hu-Jie (2018) discutem que a realização desta técnica é essencial para determinar o exato fenótipo dos MATs (Wei & Hu-Jie, 2018).…”

Section: Discussionunclassified

“…Na literatura, uma ampla variedade de marcadores para reconhecimento de macrófagos no CECO, avaliando células CD68+ (Liu et al, 2008;Lu et al, 2010;Fujii et al, 2012;He et al, 2014;Ni et al, 2015;Hu et al, 2016;Weber et al, 2016;Fang et al, 2017;Yamagata et al, 2017), células CD163+ (Fujii et al, 2012;Wang et al, 2014;He et al, 2014;Balermpas et al, 2014;Matsuoka et al, 2014;Weber et al, 2016;Hu et al, 2016;Yamagata et al, 2017), células CD11c+ (Weber et al, 2016); células CD11b+ (Balermpas et al, 2014), células MRC1+ (Weber et al, 2016) e células CD204+ (Yamagata et al, 2017). No CEC de lábio, o marcador HLA-DR também foi utilizado em investigação de população de macrófagos (Lucio et al, 2016). Em uma revisão sistemática, Alves e colaboradores (2018) observaram que em estudos avaliando a infiltração e polarização de macrófagos no CECO, o marcador CD68 é o mais utilizado para o reconhecimento de macrófagos, seguido do imunomarcador CD163, (Alves et al, 2018).…”

Section: Macrófagos Associados Ao Tumor (Mat) No Cecounclassified

“…O CD163 (cluster of differentiation 163) é uma glicoproteína de superfície celular expressa exclusivamente em células de linhagem monocíticas, sendo altamente expressos em macrófagos residentes em tecidos (Fabriek et al, 2009, Maniecki et al, 2011. O perfil imunofenotípico de macrófagos M1 é frequentemente identificado pela positividade por HLA-DR, CD11c e CD80 (Mori et al, 2011;Lucio et al, 2016;Alves et al, 2018), enquanto o fenótipo M2 pode ser identificado pelos marcadores CD163, CD11b, CD204, CD206 e MRC-1 (Weber et al, 2016;Yamagata et al, 2017;Alves et al, 2018) (Hu et al, 2016). Interessantemente, não há estudos comparativos quanto à infiltração e caracterização imunofenotipica das diversas células do sistema imune envolvidas no microambiente tumoral, como linfócitos, células dendríticas, e, especificamente, quanto à expressão de macrófagos em pacientes jovens e idosos com CECO.…”

Section: Macrófagos Associados Ao Tumor (Mat) No Cecounclassified

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Macrófagos M1 e M2 e sua relação com a angiogênese em carcinomas espinocelulares orais afetando pacientes jovens e idosos

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Macrófagos M1 e M2 e sua relação com a angiogênese em carcinomas espinocelulares orais afetando pacientes jovens e idosos. Ribeirão Preto, 2019. 74p: il.; 30 cm Dissertação de Mestrado, apresentada à Faculdade de Medicina de Ribeirão Preto/USP -Área de concentração: Patologia. ABSTRACT TEIXEIRA, LR. M1 and M2 macrophages and their relation with angiogenesis in oral squamous cell carcinoma affecting young and elderly patients. Ribeirão Preto, 2019. 74p. [Dissertação de mestrado]. Faculdade de Medicina de Ribeirão Preto, São Paulo.Oral squamous cell carcinoma (OSCC) corresponds to approximately 95% of all cases of oral cavity malignancies. The classic risk factors include smoking and alcoholism; however, immune system dysfunctions due to aging (immunoscencence) in OSCC pathogenesis are poorly studied. Comparative analyzes have been made to better characterize the profile of young and old patients affected by the OSCC, which remains controversial. Among immune cells, macrophages seem to play a fundamental role in the tumor microenvironment of several malignant neoplasms and are classified in M1 (pro-inflammatory and antitumor functions) and M2 (antiinflammatory, pro-angiogenic and pro-tumoral properties) subtypes. Several studies have shown that tumor-associated macrophages (TAMs) exhibit a pro-tumoral M2 phenotype in OSCC. However, considering immunoscencence, the profile of TAMs and their effects on angiogenesis in OSCC affecting young and elderly patients is unknown. Thus, this study analyzed by immunohistochemical technique, the frequency and location of TAMs in correlation with angiogenesis in OSCC affecting different age groups. Fifty-seven biopsies were divided into three groups (I: <40 years [n=17]; II: 40-65 years [n=20]; III: > 65 years [n=20]) and selected to compose this study, being classified morphologically following WHO (2017) recommendations. Groups I, II and III were compared for immunoexpression of CD68 and CD163 for analysis of TAMs, and CD34 (blood vessels) and D2-40 (lymphatic vessels) for evaluation of microvessel density (MVD), microvascular area (MVA) and total vascular area (TVA). Immunohistochemical analysis showed similar expression of CD68 and CD163 in the three groups (p>0.05). The evaluation of blood and lymphatic MVD, MVA and TVA also showed similar patterns, with a significant predominance (p<0.05) of blood vessels in the three groups analyzed. There was no significant correlation when evaluating macrophage and angiogenic markers. Our results show a similar profile of TAMs and angiogenesis, suggesting, instead of immunoscencence, participation of molecular mechanisms of the tumor microenvironment in the maintenance of M2-polarized macrophages and blood vessels in OSCC affecting young and elderly patients.

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

Cited by 8 publications

References 36 publications

Evaluating the Polarization of Tumor-Associated Macrophages Into M1 and M2 Phenotypes in Human Cancer Tissue: Technicalities and Challenges in Routine Clinical Practice

Evaluating the Polarization of Tumor-Associated Macrophages Into M1 and M2 Phenotypes in Human Cancer Tissue: Technicalities and Challenges in Routine Clinical Practice

Immunoexpression of human leukocyte antigen-DR in actinic cheilitis and lower lip squamous cell carcinoma

Macrófagos M1 e M2 e sua relação com a angiogênese em carcinomas espinocelulares orais afetando pacientes jovens e idosos

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