Dataset Information

The number and localization of CD68+ and CD163+ macrophages in different stages of cutaneous melanoma.

ABSTRACT: The role of tumor-associated macrophages (TAMs) in cutaneous melanoma is controversial. TAMs include immunogenic and immunosuppressive subtypes, and have distinct functions according to their microanatomical localization. Our aim was to investigate TAMs in benign, premalignant, and malignant melanocytic lesions to determine possible associations with tumor progression and clinicopathological characteristics. In total, 184 tissue samples, including benign and dysplastic nevi, in-situ melanomas, superficial (Breslow's depth <1?mm), and deep (Breslow's depth >4?mm) invasive melanomas and lymph node metastases, were analyzed for macrophage content. Samples were stained immunohistochemically for CD68 and CD163, representing all TAMs and M2-macrophages, respectively. Macrophages were counted by hotspot analysis, and assessed semiquantitatively from the tumor cell nests and stromal component of malignant cases. CD68+ and CD163+ TAMs were more abundant in invasive melanomas compared with benign nevi. The proportion of TAMs in the tumor nests was higher in deep melanomas and lymph node metastases compared with superficially invasive melanomas. High amounts of CD68+ macrophages in tumor cell nests were associated with recurrence, whereas low CD163+ macrophage proportion in tumor stroma was associated with recurrence and in primary melanomas also with poor overall survival. TAMs seem to promote tumor progression in cutaneous melanoma. In particular, CD68+ TAMs and their abundance in tumor nests were associated with poor prognostic factors. However, the correlation of low stromal CD163+ TAM proportion with a poor prognosis indicates that the role of TAMs depends on their subtype and microanatomical localization.

SUBMITTER: Salmi S

PROVIDER: S-EPMC6493694 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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The number and localization of CD68+ and CD163+ macrophages in different stages of cutaneous melanoma.

Salmi Satu S Siiskonen Hanna H Sironen Reijo R Tyynelä-Korhonen Kristiina K Hirschovits-Gerz Benjamin B Valkonen Mari M Auvinen Päivi P Pasonen-Seppänen Sanna S

Melanoma research 20190601 3

The role of tumor-associated macrophages (TAMs) in cutaneous melanoma is controversial. TAMs include immunogenic and immunosuppressive subtypes, and have distinct functions according to their microanatomical localization. Our aim was to investigate TAMs in benign, premalignant, and malignant melanocytic lesions to determine possible associations with tumor progression and clinicopathological characteristics. In total, 184 tissue samples, including benign and dysplastic nevi, in-situ melanomas, s ...[more]

PMID: 30399061

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Project description:BackgroundLymphoma-associated macrophages (LAMs) are key components in the lymphoma microenvironment, which may impact disease progression and response to therapy. There are two major subtypes of LAMs, CD68+ M1 and CD163+ M2. M2 LAMs can be transformed from M1 LAMs, particularly in certain diffuse large B-cell lymphomas (DLBCL). While mantle cell lymphoma (MCL) is well-known to contain frequent epithelioid macrophages, LAM characterization within MCL has not been fully described. Herein we evaluate the immunophenotypic subclassification, the expression of immune checkpoint molecule PD-L1, and the prognostic impact of LAMs in MCL.Materials and methodsA total of 82 MCL cases were collected and a tissue microarray block was constructed. Immunohistochemical staining was performed using CD68 and CD163, and the positive cells were recorded manually in four representative 400× fields for each case. Multiplexed quantitative immunofluorescence assays were carried out to determine PD-L1 expression on CD68+ M1 LAMs and CD163+ M2 LAMs. In addition, we assessed Ki67 proliferation rate of MCL by an automated method using the QuPath digital imaging analysis. The cut-off points of optimal separation of overall survival (OS) were analyzed using the X-Tile software, the SPSS version 26 was used to construct survival curves, and the log-rank test was performed to calculate the p-values.ResultsMCL had a much higher count of M1 LAMs than M2 LAMs with a CD68:CD163 ratio of 3:1. Both M1 and M2 LAMs were increased in MCL cases with high Ki67 proliferation rates (>30%), in contrast to those with low Ki67 (<30%). Increased number of M1 or M2 LAMs in MCL was associated with an inferior OS. Moreover, high expression of PD-L1 on M1 LAMs had a slightly better OS than the cases with low PD-L1 expression, whereas low expression of PD-L1 on M2 LAMs had a slightly improved OS, although both were not statistically significant.ConclusionsIn contrast to DLBCL, MCL had a significantly lower rate of M1 to M2 polarization, and the high levels of M1 and M2 LAMs were associated with poor OS. Furthermore, differential PD-L1 expressions on LAMs may partially explain the different functions of tumor-suppressing or tumor-promoting of M1 and M2 LAMs, respectively.

Project description:BACKGROUND:The role of tumor-associated macrophages (TAMs) in the cancer immune landscape and their potential as treatment targets or modulators of response to treatment are gaining increasing interest. TAMs display high molecular and functional complexity. Therefore their objective assessment as breast cancer biomarkers is critical. The aims of this study were to objectively determine the in situ expression and significance of TAM biomarkers (CD68, CD163, and MMP-9) in breast cancer and to identify subclasses of patients who could benefit from TAM-targeting therapies. METHODS:We measured CD68, CD163, and MMP-9 protein expression in formalin-fixed paraffin-embedded tissues of breast carcinomas represented in tissue microarray format using multiplexed quantitative immunofluorescence (QIF) in two independent Yale cohorts: cohort A-n = 398, estrogen receptor-positive (ER+) and ER- cases-and the triple-negative breast cancer (TNBC)-only cohort B (n = 160). Associations between macrophage markers, ER status, and survival were assessed. Protein expression measured by QIF was compared with mRNA expression data from the METABRIC study. RESULTS:All three macrophage markers were co-expressed, displaying higher expression in ER- cancers. High pan-macrophage marker CD68 correlated with poorer overall survival (OS) only in ER- cases of cohort A (P = 0.02). High expression of CD163 protein in TAMs was associated with improved OS in ER- cases (cohort A, P = 0.03 and TNBC cohort B, P = 0.04, respectively) but not in ER+ cancers. MMP-9 protein was not individually associated with OS. High expression of MMP-9 in the CD68+/CD163+ TAMs was associated with worse OS in ER+ tumors (P <0.001) but not in ER- cancers. In the METABRIC dataset, mRNA levels followed the co-expression pattern observed in QIF but did not always show the same trend regarding OS. CONCLUSIONS:Macrophage activity markers correlate with survival differently in ER+ and ER- cancers. The association between high co-expression and co-localization of MMP-9/CD163/CD68 and poor survival in ER+ cancers suggests that these cancers may be candidates for macrophage-targeted therapies.

Project description:Background:The exact etiology and pathogenesis of granulomatous lobular mastitis (GLM) are yet to be illuminated. This study aimed to investigate CD68, CD163-positive M2 macrophages, CD57-positive natural killer (NK) cells, and IgG4 in GLM lesion tissue to explore their correlation with the occurrence and clinical features of GLM. Methods:Surgical pathologic specimens of GLM were collected from patients admitted to Hunan Provincial People's Hospital between October, 2014 and October 2015. Based on the postoperative pathological diagnosis, the tissues were divided into 3 groups: the experimental group (GLM, n=36), control group 1 (plasma cell mastitis, PCM, n=17), and control group 2 (breast cystic hyperplasia, n=10). Immunohistochemical staining was carried out using Elivision super testing to detect CD68, CD163, CD57, and IgG4 expression in the pathological tissue samples. The relationship between clinical parameters, including age, reproductive condition, nipple retraction, and tumor size, and the expressions of CD68, CD163, CD57, and IgG4 was analyzed. Results:There was no obvious difference in the levels of CD68, CD163, and CD57 expression between the GLM group and the PCM group, although both groups had higher expression levels of expression than the breast cystic hyperplasia group (P<0.05). In the GLM group, the expression level of CD57 at 2 weeks-3 months was significantly higher than at ?2 weeks (P<0.05). The expression level of CD57 in PCM patients >2 years after lactation was significantly higher than in patients ?2 years after lactation (P<0.05). The level of IgG4 expression in GLM patients with nipple retraction was significantly higher than in those without nipple retraction (P<0.05). Conclusions:Inflammatory cells are closely linked to the occurrence of GLM and PCM. In our study, both the GLM and PCM groups had low expression of IgG4, but the expression level of IgG4 in GLM patients with inverted nipples was significantly higher than that in patients without inverted nipples. This suggests that there may be two different clinical subtypes of GLM. Furthermore, our research also found that NK cells can provide a basis for GLM clinical staging.

Project description:Although impaired myeloid-derived suppressor cells (MDSCs) recently have been studied in immune thrombocytopenia (ITP), another myeloid-derived cell population signified as M2 macrophages has not been investigated properly in ITP patients. In the present study, we intended to determine the features of circulating M2-like macrophages, to examine its relationship with MDSCs, and to explore their prognostic values in ITP.Peripheral blood mononuclear cells from healthy controls and primary ITP patients were isolated to test the circulating M2-like macrophages and MDSCs. The circulating M2-like macrophage population defined as CD68+CD163+ and circulating MDSC population as CD11b+CD33+HLA-DR- were determined by flow cytometry. Plasma inflammatory cytokines were measured by multiplex ELISA.The percentages of MDSCs were found to be expanded in newly diagnosed patients of ITP, especially among those of the complete response (CR) group (p < 0.0001). Positive linear correlation was verified between percentages of M2-like macrophages and MDSCs. The same correlation was also determined in the CR group. After treatment, the percentages of M2-like macrophages and MDSCs were both increased significantly in CR group, while those patients among the PR + NR group manifested a significant numeric decrease of MDSCs but only a moderate decrease in M2-like macrophages. MIP-1?/CCL3 was negatively correlated with M2-like macrophages while MCP-1 possessed a positive correlation with M2-like macrophages, eotaxin-1/CCL11 was negatively correlated with MDSCs and interleukin-1? (IL-1?) was found to be negatively correlated with both M2-like macrophages and MDSCs.The present findings indicated critical roles of both circulating M2-like macrophages and MDSCs in ITP. The positive correlation between them might be related to inflammatory factors-mediated bidirectional interactions or partially due to their similar background patterns during differentiation. MIP-1?/CCL3, MCP-1, eotaxin-1/CCL11 and IL-1? might play a critical role in the expansion of both M2 macrophages and MDSCs population in ITP patients, which deserves further investigation.

Dataset Information

The number and localization of CD68+ and CD163+ macrophages in different stages of cutaneous melanoma.

Publications

The number and localization of CD68+ and CD163+ macrophages in different stages of cutaneous melanoma.

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