Prognostic Value of Diametrically Polarized Tumor-Associated Macrophages in Renal Cell Carcinoma

Xu, Liang; Zhu, Yu; Chen, Lian; An, Hong‐Wei; Zhang, Weijuan; Wang, Guomin; Zhang, Lin

doi:10.1245/s10434-014-3601-1

Cited by 102 publications

(86 citation statements)

References 33 publications

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“…These studies have proved the prognostic significance of TAMs in gastric cancer; however, the diametrically opposed functional status of TAMs was beyond these investigations. A recent study in renal cell carcinoma tried to prove the prognostic significance of M1/M2 phenotypes using combined analysis of CD11c and CD206 [42]. This may be better to help elucidate the prognostic significance of diametrically polarized infiltrated macrophages.…”

Section: Discussionmentioning

confidence: 99%

Infiltration of diametrically polarized macrophages predicts overall survival of patients with gastric cancer after surgical resection

et al. 2014

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Background Tumor-associated macrophages (TAMs), the most predominant tumor-infiltrating immune cells, are emerging prognostic factors and therapeutic targets for personalized therapy against malignant neoplasms. We aimed to evaluate the prognostic significance of diametrically polarized TAMs in gastric cancer and generate a predictive nomogram to refine a risk stratification system. Methods We evaluated polarized functional status of infiltrated TAMs by immunohistochemical staining of CD68, CD11c, and CD206 in 180 consecutive gastric cancer patients from Zhongshan Hospital, Shanghai, China. Prognostic values were assessed in these patients. We created a predictive nomogram by integrating polarized TAMs with the TNM staging system for overall survival of gastric cancer patients.Results CD68 ? TAMs display polarized programs comprising CD11c ? proinflammatory macrophages (M1) and CD206 ? immunosuppressive macrophages (M2) that configure versatile infiltration files in gastric cancer. CD11c ? TAMs negatively correlated with lymph node metastasis (p = 0.012), whereas CD206 ? TAMs correlated with the Lauren classification (p = 0.031). No prognostic difference was observed for overall survival for CD68 density (high vs low, p = 0.1031), whereas high versus low CD11c density (p \ 0.0001) and low vs high CD206 density (p = 0.0105) indicate better overall survival. Multivariate Cox regression analysis identified CD11c and CD206 as independent prognostic factors (p \ 0.001 and p = 0.030, respectively), which could be integrated with the TNM staging system to generate a predictive nomogram for patient outcomes. Conclusion Infiltration of polarized TAMs, a novel identified independent prognostic factor, could be combined with the TNM stage to refine a risk stratification system and better stratify patients with different prognosis. Tipping TAMs to an antitumoral phenotype might be a promising therapeutic target for postoperative treatment.

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Section: Discussionmentioning

confidence: 99%

Infiltration of diametrically polarized macrophages predicts overall survival of patients with gastric cancer after surgical resection

et al. 2014

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“…37 Other authors investigated the intratumoral balance of polarized tumor-associated macrophages and showed that especially CD206/mannose receptor-positive macrophages (M2 type) are associated with reduced survival in RCC patients. 38 Recently, markers for human MDSC have been developed (e.g., CD14CHLA-DRlow) therefore the inclusion of myeloid cells in flow cytometric analyses would be a worthwhile approach in future studies. A higher amount of HLA-DRlow (CD13high) monocytes in the blood of RCC patients has been described already especially in late tumor stages 39 and might be the cause for poor results obtained with cancer vaccines of monocytederived dendritic cells.…”

Section: E985082-6mentioning

confidence: 99%

Immune signature of tumor infiltrating immune cells in renal cancer

et al. 2015

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Tumor-associated immune cells have been discussed as an essential factor for the prediction of the outcome of tumor patients. Lymphocyte-specific genes are associated with a favorable prognosis in colorectal cancer but with poor survival in renal cell carcinoma (RCC). Flow cytometric analyses combined with immunohistochemistry were performed to study the phenotypic profiles of tumor infiltrating lymphocytes (TIL) and the frequency of T cells and macrophages in RCC lesions. Data were correlated with clinicopathological parameters and survival of patients. Comparing oncocytoma and clear cell (cc)RCC, T cell numbers as well as activation-associated T cell markers were higher in ccRCC, whereas the frequency of NK cells was higher in oncocytoma. An intratumoral increase of T cell numbers was found with higher tumor grades (G1:G2:G3/4 D 1:3:4). Tumor-associated macrophages slightly increased with dedifferentiation, although the macrophage-to-T cell ratio was highest in G1 tumor lesions. A high expression of CD57 was found in T cells of early tumor grades, whereas T cells in dedifferentiated RCC lesions expressed higher levels of CD69 and CTLA4. TIL composition did not differ between older (>70 y) and younger (<58 y) patients. Enhanced patients' survival was associated with a higher percentage of tumor infiltrating NK cells and Th1 markers, e.g. HLA-DRC and CXCR3C T cells, whereas a high number of T cells, especially with high CD69 expression correlated with a worse prognosis of patients. Our results suggest that immunomonitoring of RCC patients might represent a useful tool for the prediction of the outcome of RCC patients.

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“…79 Similar results were reported for CD206, another M2 macrophage marker. 80 The expression of M2-TAMrelated genes such as those encoding CD163, IFN regulatory factor 4, and fibronectin 1 correlated with large tumor size and poor outcome, whereas expression of the iNOS gene, an M1-TAM-related gene, showed an inverse correlation. 78 We demonstrated expression of T-cell immunoglobulin and mucin domain-containing molecule-3 (TIM-3) on tumor cells and a positive correlation of CD204 + TAMs with shorter PFS in patients with RCC, 81 and we suggested that TIM-3 is implicated in resistance to antitumor therapy.…”

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confidence: 97%

Role of tumor‐associated macrophages in human malignancies: friend or foe?

Takeya

Komohara

2016

Pathology International

154

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Tumor-associated macrophages (TAMs) play a pivotal role in tumor growth in human malignancies. Published studies have analyzed the relationship between TAM infiltration and the prognosis of patients for many human tumors. Most studies reported a positive correlation between TAM density and a poor prognosis. Studies focusing on macrophage phenotypes emphasized the protumor role of M2 anti-inflammatory macrophages in many types of human tumors. However, TAMs influence tumor progression in various ways that depend on differences in tumor sites, histology, and microenvironments. In this review, we summarize the function of TAMs in various human malignancies by reviewing the data provided in studies of TAMs in human malignancies.

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Prognostic Value of Diametrically Polarized Tumor-Associated Macrophages in Renal Cell Carcinoma

Abstract: Intratumoral balance of diametrically polarized TAMs is a novel independent predictor for survival in patients with ccRCC. Tipping the balance toward an antitumoral phenotype might be a promising target of postoperative adjuvant therapy.

Cited by 102 publications

References 33 publications

Infiltration of diametrically polarized macrophages predicts overall survival of patients with gastric cancer after surgical resection

Infiltration of diametrically polarized macrophages predicts overall survival of patients with gastric cancer after surgical resection

Immune signature of tumor infiltrating immune cells in renal cancer

Role of tumor‐associated macrophages in human malignancies: friend or foe?

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