The role of tumor-associated macrophages in solid malignancies - an overview of current knowledge.

Tumor-associated macrophages are an important part of the tumor microenvironment. The presence of certain populations of macrophages within tumor tissue may be associated with either better or worse disease prognosis. The study of these cells is currently receiving a great deal of attention, with the most important topics of investigation raised being: the typification of subpopulations of tumor-associated macrophages; identification of the prognostic significance of population density and distribution of macrophages in the tumor microenvironment; ways to influence macrophage activity, migration and differentiation within the tumor. The answers to these questions can improve the efficiency of immunoterapy for malignancies. The presented article briefly reviews recent findings on tumor-associated macrophages in solid malignancies.

Macrophages of the subcutaneous and omental fatty tissue in obese patients: Immunohistochemical phenotyping of M2 subtypes in relation to type 2 diabetes.

BACKGROUND AND AIMS: Macrophages are linked to the initiation of the chronic inflammation believed to underlie the changes taking place in the white fatty tissue of obese people. Both the number of macrophages, but their functional status, play an important role in the development of inflammation. Classically, macrophages are divided into two types: pro-inflammatory (M1) and anti-inflammatory (M2) types, and based on current immunological studies, further views on the functional distribution of macrophages are suggested. In this study, we evaluated the M1 and M2 macrophages ratio in obese subjects with, or without diabetes. To identify all macrophages, we used CD68 expression, while CD204 expression is typically used for the M2 macrophage. MATERIALS AND METHODS: During bariatric surgery, carried out in obese people with and without type 2 diabetes (T2D), we obtained subcutaneous adipose tissue from the navel and omental adipose tissue. We also obtained the same tissue from people with a physiological range of BMI from a judicial autopsy. Applying immunohistochemical staining anti-CD68 and anti-CD204, we carried out a quantitative evaluation of the number of macrophages. RESULTS: We found CD68+ and CD204+ positive macrophages in perivascular spaces and between fat cells, both isolated and in larger infiltrates. They were also present in so-called "crown-like structures" (CLS) around dying adipocytes. Quantitative analysis showed an increased number of macrophages in all obese patients compared to the control group of non-obese, individuals without T2D. The most striking observation was the macrophage increase in the visceral fatty tissue of diabetics. The number of CD68 and CD204 positive macrophages was statistically significantly smaller in patients without T2D. CONCLUSION: We demonstrated a significantly greater number of macrophages in visceral adipose tissue, especially in patients with T2D. Our results also show a positive correlation between the presence of T2D and the total number of macrophages; a significantly greater number of macrophages were found in visceral adipose tissue, especially in patients with T2D.

M1/M2 macrophage polarization in human obese adipose tissue.

Obesity and insulin resistance are closely associated with chronic inflammation in adipose tissue, where macrophages play an important role. Adipose tissue macrophages can be divided into two main phenotypes: the classical M1 macrophages and alternatively activated macrophages M2. M1 macrophages produce pro-inflammatory cytokines (TNF-α, interleukin IL-6 and MCP-1) and thus contribute to the development of insulin resistance. On the other hand, M2 macrophages, anti-inflammatory, are involved in the maintenance of tissue homeostasis and are typical in the adipose tissue of slender individuals. Macrophages can also play a role in the pathogenesis of other serious illnesses such as cardiovascular diseases or cancer. This article reviews the latest data on macrophage polarization in adipose tissue.

Survivin in breast lesions: immunohistochemical analysis of 196 cases.

We examined the survivin expression pattern by immunohistochemistry in 43 fibroadenomas and 153 ductal carcinomas of the breast. The subcellular localization of survivin and the intensity of immunoreaction were assessed. We analyzed the differences of survivin expression between fibroadenomas and carcinomas. We also correlated the survivin expression pattern in carcinomas with other clinicomorphological parameters such as the age of patients, the grade and size of primary tumor as well as the lymph node metastasis. Overall, survivin was detected in 107/153 carcinomas (69.9%) and in 26/43 fibroadenomas (60.5%). Statistical analysis confirmed significant correlations between the assessed parameters in fibroadenomas and carcinomas. Grade of carcinomas was significantly related to survivin expression in both subcellular localization and the intensity of immunoreaction. Tumor grade 3 was associated with nuclear positivity and combined nuclear and cytoplasmic localization. Carcinomas larger than 20 mm showed nuclear and combined localization in 81% of cases and higher intensity of survivin immunoreaction was also notably related to larger carcinomas. Statistically significant differences were also observed between subcellular survivin localization and intensity of immunoreaction. Our result suggest that nuclear accumulation of survivin is associated with proliferative fenotype and survivin was shown to be a worse prognostic marker in breast ductal carcinoma.

Expression and significance of survivin in colorectal high grade and low grade adenomas.

We examined immunohistochemically the expression pattern of a potential tumor biomarker survivin in a panel of 116 tubular adenomatous polyps to determine its association with clinicomorphological parameters such as age of patients, size of polyps, degree of dysplasia and polyp localization. In each section, the subcellular localization of survivin antigen and the intensity of staining were assessed. Overall, survivin was expressed in 90 cases (77.6%). Cytoplasmic positivity was observed in 46/116 cases (39.7%), while nuclear and combined nuclear and cytoplasmic reaction in 44/116 cases (37.9%). High grade dysplasia was diagnosed in 52 cases (44.8%) and low grade dysplasia in 64 cases (55.2%). Statistical analysis revealed a significant correlation between subcellular survivin localization and the degree of dysplasia, size of polyps and colon localization. On the other hand, survivin expression pattern did not correlate with the age of patients. Statistically significant trend was confirmed between intensity of survivin immunoreaction and tumor size and dysplasia grade, and also the trend between negative/strong survivin intensity and polyp localization. Another statistically significant association was found between the degree of dysplasia and the size of polyps. Our findings revealed that survivin is frequently expressed in different subcellular compartments of adenoma cells. Our recent results suggest that the nuclear and combined nuclear and cytoplasmic survivin localizations are strongly associated with poor prognostic parameters in the assessment of colon adenomas. Thus, survivin may represent a promising biomarker in immunohistochemical evaluation of these lesions.