Tumor-associated Macrophages In Patients Research Articles

ASO Visual Abstract: Clinical Significance of SIRPα Expression on Tumor-Associated Macrophages in Patients with Lung Squamous Cell Carcinoma.

ASO Visual Abstract: Clinical Significance of SIRPα Expression on Tumor-Associated Macrophages in Patients with Lung Squamous Cell Carcinoma.

The association of appendectomy with prognosis and tumor-associated macrophages in patients with colorectal cancer

The vermiform appendix plays an important role in colorectal immunity and the homeostasis of the gut microbiome. We aimed to evaluate the prognostic value of prior appendectomy for patients with colorectal cancer (CRC). This study revealed that prior appendectomy is an independent risk factor for the prognosis of patients with CRC, based on a multicentral CRC cohort. We further demonstrated that appendectomy induced a poor prognosis of CRC through the depletion of M1 macrophage cells in AOM-induced mice, which was confirmed in age-, sex-, and location-matched patients' cohorts and orthotopic model models with the CT26 cell line. Poor responses to anti-PD-1 immunotherapy were detected in patients with CRC with appendectomy, and cetuximab is an effective treatment for patients with appendectomy-associated colorectal cancer (APD-CRC) to improve their prognosis. Our study will provide a reference for developing treatment plans for a considerable number of patients with APD-CRC, which is of great clinical significance.

Clinical Significance of SIRPα Expression on Tumor-Associated Macrophages in Patients with Lung Squamous Cell Carcinoma.

Signal-regulatory protein alpha (SIRPα) is an immune checkpoint molecule expressed on macrophages that functions to inhibit phagocytosis by binding to CD47 expressed on tumor cells. SIRPα has attracted increasing attention as a novel target for cancer immunotherapy; however, the expression and immune function of SIRPα in lung squamous cell carcinoma (LUSC) remain unclear. Therefore, this study aimed to identify the clinical importance of SIRPα expression in LUSC and to explore the factors that elevate SIRPα expression. Primary LUSC specimens surgically resected from 172 patients underwent immunohistochemical evaluation of the association of SIRPα expression on tumor-associated macrophages with clinicopathological features and clinical outcomes. Furthermore, we analyzed the association of SIRPα expression with tumor-infiltrating lymphocytes and the expression of programmed cell death ligand 1 (PD-L1). In vitro, monocytes were treated with cytokines, and SIRPα protein expression was assessed by flow cytometry. There were no differences in SIRPα expression and clinicopathological factors. High SIRPα expression was significantly associated with PD-L1-positive expression, and high CD8, PD-1, and CD163 expression. The high SIRPα expression group showed significantly shorter recurrence-free survival (RFS) and overall survival (OS). On multivariate analysis, high SIRPα expression was an independent poor prognostic factor for RFS and OS. The expression of SIRPα protein in monocytes was upregulated by treatment with IFNγ. Our analysis revealed that high SIRPα expression significantly predicts poor prognosis in patients with surgically resected LUSC.

Immunohistochemical diagnosis of tumor-associated macrophages in patients with muscle-invasive bladder cancer after radical cystectomy

BACKGROUND: Bladder cancer is a serious problem of oncourology. The gold standard of treatment for muscle-invasive bladder cancer is radical cystectomy with previous neoadjuvant chemotherapy. Unfortunately, the effectiveness of radical treatments is severely limited in the long term. For this reason, research in the field of predicting survival can significantly improve long-term oncological results. The determination of the levels of macrophages associated with the tumor appears promising.
 AIM: to determine the effect of the expression levels of macrophages associated with a tumor on survival rates in patients diagnosed with muscle-invasive bladder cancer after radical cystectomy.
 MATERIALS AND METHODS: the study was conducted on the basis of the Clinic of the Bashkir State Medical University in the period from 01.05.2021 to 01.07.2023. The study involved 66 patients with an established diagnosis of muscle-invasive bladder cancer. After surgical treatment, histological and immunohistochemical studies were performed to determine CD68 and CD163 levels. After 24 months, a survival analysis was performed to determine the levels of general, tumor-specific and relapse-free survival and the construction of Kaplan–Mayer graphs.
 RESULTS: According to the results of the analysis, there was a significant decrease in survival in groups with high CD68 and CD163 expression rates (p 0.05). In the study groups, there was a significantly significant correlation between high levels of CD68 and CD163 (p 0.05).
 CONCLUSIONS: CD68 and CD163 can act as independent markers of predicted survival in patients with muscle-invasive bladder cancer after radical cystectomy.

Commentary on the publication of Yargunin S.A. et al. “Dynamics of changes in tumor-associated macrophages in patients with primary skin melanoma depending on the method of surgical treatment”

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Dynamics of changes in tumor-associated macrophages in patients with primary skin melanoma depending on the method of surgical treatment

Summary: Skin melanoma is one of the deadliest among human skin tumors, and surgery remains the first and main method in its combined treatment. Despite the seemingly radical nature of surgical interventions in patients with primary skin melanoma, the frequency of locoregional recurrence and metastasis remains high. The question of the impact of surgical treatment on the evolution of the melanoma microenvironment remains unclear.Aim: to investigate the dynamics of polarization in tumor-associated macrophages in patients with primary skin melanoma of stage 0-IIa and in subsequent metastatic lesions to assess the impact of postoperative ischemia on survival of patients.Results: it was found that in patients with primary skin melanoma of stage 0-IIa plastic replacement of a tissue defect, compared with conventional suturing, can lead to a decrease in the density in the intrastromal distribution of pro-inflammatory CD68 + macrophages in the surgical focus, as well as less frequent polarization of TAM cells in the M2 direction and migration to the intrastromal component of the tumor, their more frequent mixed content, which, as a result, affects the survival of this category of patients for the better.Conclusions: plastic closing a surgical defect in patients with primary skin melanoma of stage 0-IIa may affect the duration of postoperative ischemia and the polarization of TAM cells. Plastic replacement of a tissue defect after tumor removal improves five-year survival rates (PFS by 22,6 % (p = 0.003) and OS by 13,1% (p = 0.029).

Retraction: Clinicopathologic and prognostic significance of tumor-associated macrophages in patients with hepatocellular carcinoma: A meta-analysis.

Retraction: Clinicopathologic and prognostic significance of tumor-associated macrophages in patients with hepatocellular carcinoma: A meta-analysis.

Prognostic significance of tumor-associated macrophages in patients with nasopharyngeal carcinoma: A meta-analysis.

Background:To explore the prognostic value of diverse subsets of tumor-associated macrophages (TAMs) in prognosis in patients with nasopharyngeal carcinoma (NPC) using meta-analysis.Methods:Relevant studies were searched in the database of PubMed, Web of Science, Embase, Cochrane Library, Scopus, China National Knowledge Infrastructure (CNKI), and Wanfang till November 2019. The relationship between TAMs and survival outcomes was estimated by pooling hazard ratios (HRs) and 95% confidence intervals (CIs); and the correlation of TAMs and clinicopathological factors was evaluated by using odds ratios (ORs) and 95%CIs.Results:Six studies with 1549 patients were included in this meta-analysis. The high expression of CD68+ TAMs was associated with favorable disease-free survival (DFS) (HR = 0.66, 95%CI = 0.50–0.88, P = .005), whereas the density of M2-like TAMs (CD163+, CD68+CCL18+, and CD206+) was correlated to poor overall survival (OS) (HR = 1.77, 95%CI = 1.22–2.56, P = .003) and DFS (HR = 1.96, 95%CI = 1.00–3.85, P = .050) in patients with NPC.Conclusions:CD68+ TAM density is associated with superior DFS, while CD163+ M2-like TAMs predicted poor prognosis in patients with NPC.

The prognostic and clinicopathological value of tumor-associated macrophages in patients with colorectal cancer: a systematic review and meta-analysis.

There is a growing literature on the significance of tumor-associated macrophages (TAMs) in colorectal cancer (CRC). However, the role of TAMs in predicting the prognosis of CRC remains controversial. The current study aims to determine the prognostic and clinicopathological value of different types and distribution of TAMs in CRC. A comprehensive literature search of PubMed, Embase, and Cochrane Library databases was conducted from the inception to 1 September 2019. The correlations of TAMs with overall survival (OS), disease-free survival (DFS), cancer-specific survival (CSS), and clinicopathological characteristics were analyzed. A total of 5,575 patients from 29 studies were included in this meta-analysis. The pooled hazard ratios (HRs) indicated that high density of pan-macrophages in tumor invasive margin (IM) was associated with better OS (HR = 0.57, 95%CI = 0.38-0.85), DFS (HR = 0.32, 95%CI = 0.19-0.52), and CSS (HR = 0.56, 95%CI = 0.41-0.77). Moreover, the high density of pan-macrophages in tumor center (TC) was correlated with better DFS (HR = 0.66, 95%CI = 0.45-0.96). However, high expression of M2 macrophages in TC was associated with poor DFS (HR = 2.42, 95%CI = 1.45-4.07) and CSS (HR = 1.74, 95%CI = 1.24-2.44). High M2 macrophages density in IM was also associated with short DFS (HR = 2.81, 95%CI = 1.65-4.77). In addition, the results showed that high density of pan-macrophages in IM was associated with no tumor metastasis, while high M2 macrophages density in TC was correlated with poor tumor differentiation. High Pan-TAMs density in IM has a positive effect on the prognosis of CRC patients, while high density M2 macrophage infiltration in TC is a strong indicator of poor prognosis.

GATA3 as a master regulator for interactions of tumor-associated macrophages with high-grade serous ovarian carcinoma

High-grade serous ovarian carcinoma (HGSOC) is the most lethal gynecologic cancer. Emerging evidence suggests that tumor-associated macrophages (TAMs) play an immunosuppressive role in the tumor microenvironment and promote tumor growth, angiogenesis, and metastasis in ovarian cancer. Therefore, targeting TAMs in patients with ovarian cancer is an appealing strategy; however, all trials to date have failed. To improve the efficacy of this approach, we sought to elucidate the underlying mechanisms of the role of TAMs in ovarian cancer. We found that the developmental transcription factor GATA3 was highly expressed in HGSOC cell lines but not in the fallopian tube, which is the main origin of HGSOC. GATA3 expression was associated with poor prognosis in HGSOC patients (P < .05) and was found to promote proliferation and migration in HGSOC cell lines. GATA3 was released abundantly from TAM cells via exosomes and contributed to tumor growth in the tumor microenvironment. Moreover, GATA3 acted as a regulator for macrophage polarization and interactions between TAMs and HGSOC to support proliferation, motility, and cisplatin chemoresistance in mutant TP53 HGSOC cell lines. Furthermore, GATA3 played a critical role in the interactions between TAMs and mutant TP53 HGSOC to promote angiogenesis and epithelial-mesenchymal transition with epigenetic regulation. Targeting GATA3 using GATA3siRNA in TAMs impeded GATA3-driven proliferation, migration, cisplatin chemoresistance, and angiogenesis in mutant TP53 HGSOC cell lines. Our findings indicate that GATA3 plays a novel role in immunoediting of HGSOC and demonstrate that GATA3 may serve as a prognostic marker for HGSOC and a promising target in the treatment of HGSOC.

Clinicopathologic and prognostic significance of tumor-associated macrophages in patients with hepatocellular carcinoma: A meta-analysis.

Tumor-associated macrophages (TAMs) deserve more focus because of its clinicopathologic and prognostic roles in solid tumors. However, the prognostic value of TAMs in patients with hepatocellular carcinoma (HCC) is still controversial. We performed a meta-analysis to resolve the issue. We selected relevant studies from the Cochrane Library, Embase and PubMed databases. The hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated employing fixed-effect or random-effect models depending on the heterogeneity of the included trials. Moreover, we also performed subgroup analysis, cumulative meta-analysis, sensitivity analysis, and bias analysis (Egger's test). A total of 20 observational studies with 4297 patients were enrolled. For TAMs subsets, high density of CD68+ TAMs in either intratumor (IT) (pooled HR = 1.417; 95% CI = 1.092-1.839; P = 0.009) or peritumor (PT) (pooled HR = 1.393; 95% CI = 1.022-1.899; P = 0.036) was associated with a poor OS. High density of CD68+ TAMs in IT was also associated with high AFP value, large tumor size, absent encapsulation, present vascular invasion, and later tumor-nodes-metastasis (TNM) stage. High density of CD163+ macrophages in serum was associated with a poor OS (pooled HR = 5.698; 95% CI = 3.062-10.603; P < 0.001). High density of CD204+ TAMs in IT was associated with a poor OS (pooled HR = 1.947; 95% CI = 1.387-2.733; P < 0.001. High density of CD206+ TAMs in IT was associated with a poor OS (pooled HR = 1.723; 95% CI = 1.308-2.270; P < 0.001) and DFS (pooled HR = 1.711; 95% CI = 1.214-2.412; P = 0.002). However, high density of CD169+ TAMs in IT was associated with a good OS (pooled HR = 0.471; 95% CI = 0.343-0.647; P = 0.037). TAMs could serve as independent predictive indicators and therapeutic targets for HCC. Further trials are needed to elucidate the exact relationship and the underlying mechanism.

Prognostic implications of tumor associated macrophages (TAMs) in soft tissue sarcoma.

e22548 Background: Clinical responses in patients with soft tissue sarcoma administered immune checkpoint inhibitors have been infrequent. Little is known regarding the immune microenvironment in soft tissue sarcoma that leads to a lack of effective responses with immune therapies. Whilst several studies have shown T cell infiltration in sarcomas, these tumors do not respond to immunotherapies. Macrophages are important regulators of immune responses in the tumor microenvironment. Studies in mouse models indicate that macrophages regulate immune checkpoint inhibitor response. With the overall goal of developing more effective combination immunotherapies for sarcoma, we examined tumor associated macrophages in patients with soft tissue sarcoma administered neoadjuvant chemotherapy. Interactions between macrophage infiltration, tumor immunogenicity and overall survival were also assessed using publicly available RNAseq and exome mutation data. Methods: Immunohistochemistry was performed on formalin fixed soft tissue sarcoma tissue. Tissues from 20 patients with soft tissue sarcoma pre and post neo-adjuvant chemotherapy were included. TAMs were detected by CD68; M2 subtype were detected by CD163. CD4, CD8, and CD25 T cells were also examined. The density of CD68+ TAMs, CD163+ TAMs and the ratio of CD163+ TAMs / CD68+ TAMs were calculated and their correlation with survival was also made. Publicly available RNAseq and exome mutation data were assembled from The Cancer Genome Atlas (TCGA) sarcoma cohort (n = 259). For each tumor, a relative measure of abundance of tumor-infiltrating macrophages was estimated using gene expression. Tumor mutational burden (TMB), expressed as the rate of non- synonymous mutations per megabase of sequenced DNA, was used as a measure of tumor immunogenicity. Interactions between macrophage infiltration, tumor immunogenicity and overall survival were assessed by Cox regression and Kaplan-Meier analysis. Categorical relationships involving clinical, immunologic, and genomic features of the tumor immune subclasses were compared. Results: Specific alteration in the density of CD68+ TAMs, CD163+ TAMs, and the CD163 / CD68 ratio were observed in patients with soft tissue sarcoma responding to neoadjuvant chemotherapy. Categorical relationships involving macrophage infiltration, TMB, and survival were also observed. Conclusions: These study support the targeting of tumor associated macrophages in patients with soft tissue sarcoma and suggest that changes in TAMs may be achievable using neoadjuvant chemotherapy.

In Vivo MR Imaging of Tumor-Associated Macrophages: The Next Frontier in Cancer Imaging.

There is a complex interaction between cancer and the immune system. Tumor-associated macrophages (TAMs) can be subverted by the cancer to adopt a pro-tumor phenotype to aid tumor growth. These anti-inflammatory, pro-tumor TAMs have been shown to contribute to a worsened outcome in several different types of cancer. Various strategies aimed at combating the pro-tumor TAMs have been developed. Several therapies, such as oncolytic viral therapy and high-intensity focused ultrasound, have been shown to stimulate TAMs and suppress tumor growth. Targeting TAMs is a promising way to combat cancer, but sensitive imaging methods that are capable of detecting these therapeutic responses are needed. A promising idea is to use imaging contrast agents to label TAMs to determine their relative number and location within, and around the tumor. This can provide information about the efficacy of TAM depletion therapies, as well as macrophage-stimulating therapies. In this review, we describe various in vivo MRI methods capable of tracking TAMs, and conclude with a short section on tracking TAMs in patients.

Prognostic value of diametrically polarized tumor-associated macrophages in multiple myeloma.

Tumor-associated macrophages (TAMs) are correlated with the prognosis of different types of solid tumors and lymphoma, according to many clinical studies. In vitro experiments have demonstrated the roles of these cells in myeloma cell survival, angiogenesis, immunomodulation, drug resistance, and the interaction between malignant myeloma cells and the microenvironment. Here, we investigated the prognostic significance of TAMs in patients with multiple myeloma (MM). We evaluated the polarized functional status of bone marrow infiltrated by TAMs by immunohistochemical staining of CD68, iNOS, and CD163 in 240 patients with MM from January 2009 to December 2014. The overall response rates to chemotherapy were lower in patients with high CD68+ or CD163+ TAM densities than in those with low densities. Kaplan-Meier analysis showed that the progression-free survival (PFS, p = 0.001) and overall survival (OS, p < 0.001) of patients with low CD163+ TAM density were significantly higher than those of patients with high CD163+ TAM density. Furthermore, combined analysis of iNOS+ and CD163+ TAMs (iNOS/CD163 signature) exhibited greater power in predicting patient outcomes for both PFS (p < 0.001) and OS (p < 0.001). Moreover, Cox regression analysis identified iNOS+ and CD163+ TAMs as independent prognostic factors (p = 0.007, p < 0.001, respectively). These factors could be combined with the international staging system (ISS) to generate a predictive nomogram for patient outcomes. Our findings suggest that the mosaic of diametrically polarized TAMs is a novel independent prognostic factor that could be integrated into the evaluation of and therapy for MM.

578 Immunomodulatory effects of bexarotene on tumor-associated macrophages in patients with mycosis fungoides

578 Immunomodulatory effects of bexarotene on tumor-associated macrophages in patients with mycosis fungoides

The Prognostic and Clinicopathological Significance of Tumor-Associated Macrophages in Patients with Gastric Cancer: A Meta-Analysis.

ObjectiveComprehensive studies have investigated the prognostic and clinicopathological value of tumor-associated macrophages (TAMs) in gastric cancer patients, yet results remain controversial. Therefore, we performed a meta-analysis to clarify this issue.MethodsPubMed, Embase, and the Cochrane Library databases were searched to identify eligible studies. We extracted hazard ratios (HRs) and odds ratios (ORs) with their corresponding 95% confidence intervals (95% CIs) to estimate the effect sizes. In addition, subgroup analysis and sensitivity analysis were also conducted.ResultsA total of 19 studies involving 2242 patients were included. High generalised TAMs density was significantly associated with poor overall survival (OS) (HR 1.49, 95% CI 1.15–1.95). Subgroup analysis revealed that CD68+ TAMs had no significant effect on OS (HR 1.38, 95% CI 1.00–1.91). High M1 TAMs density was correlated with better OS (HR 0.45, 95% CI 0.32–0.65). By contrast, high density of M2 TAMs was correlated with a poor prognosis for OS (HR 1.48, 95% CI 1.25–1.75). Furthermore, high M2 TAMs density was correlated with larger tumor size, diffuse Lauren type, poor histologic differentiation, deeper tumor invasion, lymph node metastasis, and advanced TNM stage.ConclusionsOverall, this meta-analysis reveal that although CD68+ TAMs infiltration has the neutral prognostic effects on OS, the M1/M2 polarization of TAMs are predicative factor of prognosis in gastric cancer patients.

Abstract 2371: The number of CD163-positive cells in the microenvironment and peripheral blood lymphocyte-to-monocyte-ratio (LMR) is associated with poor outcome in patients with diffuse large B-cell lymphoma (DLBCL)

Abstract Purpose: Despite advances in treatment, 30-40% of the DLBCL patients succumb to their disease. The prognostic role of peripheral blood absolute monocyte count (AMC), LMR and tumor-associated macrophages (TAM) in DLBCL has previously been suggested. However, information on the association of LMR/AMC and TAM is limited. We performed this study to evaluate the association and prognostic role of LMR/AMC and TAM in patients with DLBCL treated at our institute. Patients and Method: 76 patients with newly diagnosed DLBCL were selected. CD163 expression was assessed by immunohistochemistry using tissue microarray. The number of CD163 positive nucleated cells at objective magnification of 40x were counted and were divided into 4 categories: score 0 (0-25 cells); score 1 (26-50); score 2 (51-75); score 3 (&amp;gt;75). Results: The median age of the patients was 62 (range: 27-87) years-old. 38 patients (52.4%) were advanced stage (stage 3/4), and 47.3% of patients had germinal center (GC) phenotype. The median AMC at the time of diagnosis was 408 (range: 42-1,107)/mm3, and the median LMR was 2.94 (0.64-14.06). CD163 staining was scored as follows: score 0: 13 patients (17.1%), score 1: 7 patients (9.2%), score 2: 6 patients (7.9%), score 3: 50 patients (65.8%). There was a trend for higher stage (p = 0.08) and non-GC type histology (p = 0.05) in patients with CD163 score 3. Although there was no difference in AMC between those with CD163 score 0-2 and 3, CD163 score 3 was significantly associated with lower LMR (LMR&amp;lt;2.77; p = 0.011). Of the patients who received treatment (n = 68), 43.4% of the patients were treated with a rituximab containing regimen (R(+)). 16 (R(+):5, R(-):11) patients died after a median observation of 6.2 (0.1-21.6) years. LMR&amp;lt;2.77, and CD163 score 3 were associated with adverse prognosis in R(-) patients (p = 0.0032, 0.0084) but not in R(+) (p = 0.92, 0.37) patients. Conclusion: We have confirmed in our patients with newly diagnosed DLBCL who received chemotherapy without rituximab, that LMR and the number of CD163-positive cells are significant prognostic factors. Contrary to previous reports, neither TAM as characterized by CD163-positive cells in the microenvironment or LMR/AMC were prognostic factors in R(+) patients. Of interest, higher number of TAM was associated with lower LMR. Further evaluation is needed to confirm this finding and its clinical relevance. Citation Format: Eri Matsuki, Olga L. Bohn, Janine Pichardo, Andrew Zelenetz, Anas Younes, Julie Teruya-Feldstein. The number of CD163-positive cells in the microenvironment and peripheral blood lymphocyte-to-monocyte-ratio (LMR) is associated with poor outcome in patients with diffuse large B-cell lymphoma (DLBCL). [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2371. doi:10.1158/1538-7445.AM2015-2371

Expression of Cathepsin L in tumor cells and tumor-associated macrophages in patients with Ewing sarcoma family of tumors: a pilot study.

Cysteine protease Cathepsin L is involved in bone remodeling and expressed in activated macrophages. It is highly expressed in metastatic tumor tissue, especially with bone metastases. We evaluated immunohistochemical expression of Cathepsin L in tumor cells and tumor-associated macrophages (TAMs) in chemo-naive Ewing sarcoma. Retrospective evaluation of archived specimens of Ewing sarcoma. Immunohistochemical staining was performed on archived blocks of chemo-naive patients with Ewing sarcoma treated with uniform chemotherapy at our institute between January 2009 and November 2011. Immunohistochemical expression was co-related with baseline demographics and survival. During the study period, we had evaluable baseline samples from 62 patients with median age 15 years (range: 2-40); 26 (42%) had metastases. Cathepsin L expression in tumor cells was observed in 8/62 (13%) specimens. None of the baseline clinical characteristics correlated with Cathepsin L expression. Cathepsin L positivity was associated with poor response to neoadjuvant chemotherapy (NACT) (P = 0.05), but did not influence either event-free-survival (EFS) or overall survival. Cathepsin L was expressed in TAMs in all specimens. Grade 3 TAMs (>10 TAMs/high power field) was associated with better response to NACT (P = 0.05). On univariate analysis Grade 3 TAMs predicted superior EFS (median EFS 28.5 months in those with Grade 3 TAMs versus 14.8 months in those with grade ½ TAMs [P = 0.04]). Cathepsin L expression by immunohistochemistry was low in our patient cohort, and it did not affect the outcome. In addition, Grade 3 TAMs with Cathepsin L expression was associated with improved EFS.

High infiltration of tumor-associated macrophages in triple-negative breast cancer is associated with a higher risk of distant metastasis.

BackgroundTriple-negative breast cancer (TNBC) is associated with poor prognosis and high probability of distant metastases. Tumor microenvironments play a pivotal role in tumor metastasis. Tumor-associated macrophages (TAMs) are one of the main cell components, and they are correlated with increasing metastatic risk. The aim of this study is to analyze the prognostic significance of the infiltration of TAMs in patients with TNBC.Materials and methodsImmunohistochemical staining for cluster of differentiation (CD)68 (a marker for macrophages) was performed on tissue microarrays of operable breast cancer among 287 patients with TNBC, and the number of infiltrating TAMs was correlated with clinicopathological parameters.ResultsWe found that TNBC with a large number of infiltrating TAMs had a significantly higher risk of distant metastasis, as well as lower rates of disease-free survival and overall survival than those with a smaller number of infiltrating TAMs. Multivariate analysis indicated that the number of infiltrating TAMs was a significant independent prognostic factor of disease-free survival (P=0.001) in all patients.ConclusionOur results suggested that high infiltrating TAMs are a significantly unfavorable prognostic factor for patients with TNBC, and they could become a potentially useful prognostic marker for TNBC.

Histological characterization of tumor-associated macrophages in patients with different stages of hepatocellular carcinoma (HCC) (TUM4P.914)

Abstract Tumor-associated macrophages, major leukocytes detected in tumor tissues, have been characterized as M2Mφ. Recently, M2Mφ have been classified into different subsets; M2aMφ, M2bMφ and M2cMφ. Therefore, in this study, the subset of M2Mφ present in tumor tissues of HCC patients was determined. Tumor tissues were obtained by liver biopsy and liver resection from patients with early and advanced stages of HCC. Paraffin embedded tissue specimens were stained for PE-conjugated anti-CD68 Ab. Also, the same tissue specimens were stained for FITC-conjugated anti-IL-12 Ab, PE-conjugated anti-IL-10 Ab, FITC-conjugated anti-CCL1 Ab, and FITC-conjugated anti-CD206 Ab. Stained histologic specimens were examined microscopically. In the results, large numbers of CD68+cells were predominantly present in the edge of the tumors. Large numbers of Mφ were not isolated from the tumor nests. CD68+cells isolated from advanced stage HCC patients were determined as IL-10+CD206+ cells, while a few numbers of these cells were demonstrated in the tumor tissues of early stage HCC patients. IL-10+CCL1+ cells and IL-12+CD68+ cells were not isolated from both advanced stage and early stage HCC patients. These results indicate that a majority of M2Mφ present in advanced stage HCC patients are M2aMφ and/or M2cMφ.