Prognostic Impact of CD163+ Macrophages in Tumor Stroma and CD8+ T-Cells in Cancer Cell Nests in Invasive Extrahepatic Bile Duct Cancer

Miura, Takuya; Yoshizawa, Tadashi; Hirai, Hideaki; Seino, Hiroko; Morohashi, Satoko; Wu, Yunyan; Wakiya, Taiichi; Kimura, Norihisa; Kudo, Daisuke; Ishido, Keinosuke; Toyoki, Yoshikazu; Kijima, Hiroshi; Hakamada, Kenichi

doi:10.21873/anticanres.11304

Cited by 44 publications

(35 citation statements)

References 27 publications

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“…It possesses potent antitumor immune function that could inhibit progression of several tumors [ 14 ], and elevated level of lymphocyte was reported to be associated with favorable prognosis of a variety of tumors [ 15 ]. It was also reported that several subtypes of tumor infiltrating lymphocyte were associated with better outcomes of a variety of tumors [ 16 – 18 ], including CD8+ T cells [ 19 ] and memory T cells [ 20 ]. However, some subsets of T cells were associated with progression and unfavorable prognosis of tumors, such as regulatory T cells [ 21 ] and Th17 cells [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

Low lymphocyte count and high monocyte count predicts poor prognosis of gastric cancer

et al. 2018

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BackgroundExisting data about the prognostic value of absolute count of blood cells in gastric cancer was limited. Thus, the present study aims to investigate the prognostic value of absolute count of white blood cell (WBC), neutrophil, lymphocyte, monocyte and platelet in gastric cancer patients.MethodsFrom September 2008 to March 2015, 3243 patients treated with radical gastrectomy were enrolled in the present study. Clinicopathological characteristics were recorded. The prognostic value of blood test in gastric cancer patients were analyzed.ResultsThere were 2538 male and 705 female. The median age was 58 years (range 20–90). The median follow-up time was 24.9 months (range 1–75). The 1-, 3- and 5-year overall survival rate was 88.9%, 65.8% and 57.2%, respectively. The optimal cut off value was 6.19 × 109/L for WBC (P = 0.146), 4.19 × 109/L for neutrophil (P = 0.004), 1.72 × 109/L for lymphocyte (P = 0.000), 0.51 × 109/L for monocyte (P = 0.019) and 260.0 × 109/L for platelet (P = 0.002), respectively. Neutrophil, lymphocyte, monocyte and platelet were risk factors for the prognosis of gastric cancer (all P < 0.05). However, only lymphocyte and monocyte were independent risk factors (both P < 0.05). Combination of lymphocyte and monocyte could increase the prognostic value for gastric cancer patients, especially in stage II/III gastric cancer patients.ConclusionsHigh absolute count of neutrophil, monocyte and platelet, and low absolute count of lymphocyte were associated with poor prognosis of gastric cancer. However, only lymphocyte and monocyte count were independent prognostic predictors. Combination of lymphocyte and monocyte count could further increase the predictive value for gastric cancer.

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Section: Discussionmentioning

confidence: 99%

Low lymphocyte count and high monocyte count predicts poor prognosis of gastric cancer

et al. 2018

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“…TAMs at different locations within the tumor may have different impacts on GC progression [ 14 ]. TAMs infiltration into tumor stroma has significant clinical relevance in GC, indicating the importance of not only studying the number but also studying the locations [ 15 ]. TAMs infiltration at invasive front could influence cancer metastasis through epithelial-mesenchymal transition (EMT) mechanism [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Distribution pattern of tumor associated macrophages predicts the prognosis of gastric cancer

et al. 2017

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PurposeAs mayor biomarkers in tumor microenvironment (TME), tumor associated macrophages (TAMs) of gastric cancer (GC) still needs further studies in terms of the number and distribution pattern.MethodsHerein, tissue microarrays (TMA) incorporating 494 GC surgical samples in duplicate were stained for TAMs infiltration analysis. TAMs number was counted according to the locations, including infiltrating macrophages in cancer nest (MC), in invasive front (MF) and in stroma (MS). Correlations between TAMs number, distribution pattern and clinic-pathological features and survival analyses were performed.ResultsInfiltrating macrophages number in GC tissues was much higher than that in peritumoral tissues. TAMs number was not significantly correlated with the overall survival (OS). TAMs distribution pattern could be categorized into MC or MF/MS dominant pattern, and correlated with histological grade (P =0.001). The median OS of MF/MS dominant pattern (22.1, 95%CI: 23.5-28.9) was significantly shorter than that of MC dominant pattern (25.6, 95%CI: 28.5-35.6) (P =0.002). By receiver operating characteristic curve (ROC) analysis, the predictive value of TAMs distribution pattern was superior to histological grade and pM stage, but inferior to pN and TNM stage.ConclusionsTAMs distribution pattern could be an independent prognostic factor for the OS of GC patients, and patients with MF/MS dominant pattern had worse outcomes.

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“…Thus, TAMs facilitate tumor regrowth, revascularization, spread after the treatment 30,31 . Their tumor-promoting functions are supported by clinical association of TAM infiltration with poor prognosis in most human cancer types, including ovarian cancer [32][33][34] . Therefore, various strategies have been developed to exploit TAMs for anti-cancer therapies 25,35 .…”

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confidence: 99%

Potent BRD4 inhibitor suppresses cancer cell-macrophage interaction

et al. 2020

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Small molecule inhibitor of the bromodomain and extraterminal domain (BET) family proteins is a promising option for cancer treatment. However, current BET inhibitors are limited by their potency or oral bioavailability. Here we report the discovery and characterization of NHWD-870, a BET inhibitor that is more potent than three major clinical stage BET inhibitors BMS-986158, OTX-015, and GSK-525762. NHWD-870 causes tumor shrinkage or significantly suppresses tumor growth in nine xenograft or syngeneic models. In addition to its ability to downregulate c-MYC and directly inhibit tumor cell proliferation, NHWD-870 blocks the proliferation of tumor associated macrophages (TAMs) through multiple mechanisms, partly by reducing the expression and secretion of macrophage colonystimulating factor CSF1 by tumor cells. NHWD-870 inhibits CSF1 expression through suppressing BRD4 and its target HIF1α. Taken together, these results reveal a mechanism by which BRD4 inhibition suppresses tumor growth, and support further development of NHWD-870 to treat solid tumors.

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Prognostic Impact of CD163+ Macrophages in Tumor Stroma and CD8+ T-Cells in Cancer Cell Nests in Invasive Extrahepatic Bile Duct Cancer

Cited by 44 publications

References 27 publications

Low lymphocyte count and high monocyte count predicts poor prognosis of gastric cancer

Low lymphocyte count and high monocyte count predicts poor prognosis of gastric cancer

Distribution pattern of tumor associated macrophages predicts the prognosis of gastric cancer

Potent BRD4 inhibitor suppresses cancer cell-macrophage interaction

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