Tumor-associated macrophages and the profile of inflammatory cytokines in oral squamous cell carcinoma

Costa, Nádia Lago; Valadares, Marize Campos; Souza, Pedro Paulo Chaves de; Mendonça, Elismauro Francisco; Oliveira, José Carlos de; Silva, Tarcı́lia Aparecida; Batista, Aline Carvalho

doi:10.1016/j.oraloncology.2012.09.012

Cited by 136 publications

(109 citation statements)

References 21 publications

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“…Taken together, these findings indicate the pro-tumor profile of M2 macrophages since this phenotype promotes angiogenesis and extracellular matrix remodeling by expressing metalloproteinases, conditions that favor neoplastic dissemination. 12,14,15,17,19,22 In contrast to previous studies on OSCC, the present results suggest that M2 TAMs may play a more important role in early stages of lip carcinogenesis. During these stages in which tumors are possibly more immunogenic, neoplastic cells may promote an immunosuppressive microenvironment in order to escape immune surveillance.…”

Section: Discussioncontrasting

confidence: 99%

“…11,12 Thus, the predominance of one subtype over the other may explain differences in the biological behavior of different neoplasms and/or in the molecular mechanisms of immune escape. 12,14 In the present study, both macrophage subtypes, M1 and M2, were detected along the invasive front in SCCLL. A predominance of M2 over M1 TAMs was observed in tumors without regional lymph node metastasis and in early-stage tumors (p = 0.009).…”

Section: Discussionsupporting

confidence: 58%

“…In contrast, using immunohistochemistry, Li et al, 23 Liu et al, 24 and Marcus et al 25 demonstrated a significant association between TAMs and the development of clinically positive lymph nodes in oral and oropharyngeal SCC. Furthermore, Costa et al 14 observed a predominance of M2 TAMs in cases of OSCC with regional nodal metastasis when compared to OSCC without metastasis.…”

Section: Discussionmentioning

confidence: 98%

“…This immunosuppressive capacity is a consequence of the production of anti-in flammatory and immunosuppressive cytokines such as IL-10 and transforming growth factor beta (TGF-β), inhibition of the inflammatory and cytotoxic functions of M1 macrophages, and induction of angiogenesis and tissue remodeling and repair, conditions that favor tumor growth and dissemination. 12,13,14,15,16,17,18,19,20,21,22 Although studies have suggested a significant association between TAMs and poor prognosis in patients with oral squamous cell carcinoma (OSCC), 14,15,23,24,25,26 little is known about these macrophage phenotypes in SCCLL. Therefore, the objective of the present study was to investigate the presence of TAM subpopulations M1 and M2 in cases of SCCLL and to evaluate the possible role of these subtypes in the development of regional lymph node metastasis and their association with clinical and pathological features of the tumor.…”

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confidence: 99%

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

et al. 2016

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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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Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 58%

Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 99%

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

et al. 2016

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“…Costa et al (2013) showed a predominance of M2 phenotype in the tumor microenvironment of oral cavity squamous cell carcinoma characterized by higher percentage of macrophages expressing IL-10 and TGF-β compared with healthy individuals. The predominance of M2 phenotype was related to local immunosuppression and reduced survival.…”

Section: Ajimentioning

confidence: 94%

Immunological Processes in Cancer: A Link Between Inflammation and Immunity

Victorino¹

2014

American Journal of Immunology

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Cancer is a worldwide issue and one of the most relevant death causes in child and adults. There are several causes that can lead to cancer development. It is well known that inflammation is one known hallmark of cancer and it favors tumor cells growth. Several alterations in immunological and inflammatory processes are caused in response to tumor presence and both innate and adaptive immunity have effective mechanism to destroy tumor cells. Nevertheless, distinct tumor types developed mechanisms to evade anti-tumor immunological responses. Here, we revise researches regarding inflammation and immune response during cancer development, as well as cancer signaling pathways and immunotherapy that have been performed in Brazil. The better understanding of the mechanisms regarding cancer and immunological processes is of huge importance and it may support the development of new cancer targets.

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RACK1 promotes cancer progression by increasing the M2/M1 macrophage ratio via the NF‐κB pathway in oral squamous cell carcinoma

et al. 2020

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Receptor for activated C kinase 1 (RACK1) has been shown to promote oral squamous cell carcinoma (OSCC) progression, and RACK1 expression levels have been negatively correlated with prognosis in patients with OSCC. Here, we investigated the impact of RACK1 OSCC expression on the recruitment and differentiation of tumor‐associated macrophages. High RACK1 expression in OSCC cells correlated with increased M2 macrophage infiltration in tumor samples from a clinical cohort study. Moreover, the combination of RACK1 expression and the M2/M1 ratio could successfully predict prognosis in OSCC. OSCC cells with high RACK1 expression inhibited the migration of THP‐1 cells, promoted M2‐like macrophage polarization in vitro, and increased the proportion of M2‐like macrophages in a xenograft mouse model. Moreover, both M1‐ and M2‐like macrophage polarization‐associated proteins were induced in macrophages cocultured with RACK1‐silenced cell supernatant. A mechanistic study revealed that the expression and secretion of C‐C motif chemokine 2 (CCL2), C‐C motif chemokine 5 (CCL5), interleukin‐6 (IL‐6), and interleukin‐1 (IL‐1) are closely related to RACK1 expression. In addition, blocking nuclear factor‐kappa B (NF‐κB) could promote M2‐like macrophage polarization. These results indicate that RACK1 and the M2/M1 ratio are predictors of a poor prognosis in OSCC. RACK1 promotes M2‐like polarization by regulating NF‐κB and could be used as a potential therapeutic target for antitumor immunity.

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Tumor-associated macrophages and the profile of inflammatory cytokines in oral squamous cell carcinoma

Cited by 136 publications

References 21 publications

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

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

Immunological Processes in Cancer: A Link Between Inflammation and Immunity

RACK1 promotes cancer progression by increasing the M2/M1 macrophage ratio via the NF‐κB pathway in oral squamous cell carcinoma

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