LSC - 2017 - Reprogramming Of Tumor Associated Macrophages By Modulating Wnt/ß-catenin Signalling In Lung Cancer

Sarode, Poonam; Zheng, Xiang; Weigert, Andreas; Tretyn, A; Pullamsetti, Soni Savai; Seeger, Werner; Savai, Rajkumar

doi:10.1183/1393003.congress-2017.oa4859

Cited by 3 publications

(3 citation statements)

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“…Researchers are optimistic that by therapeutic manipulation, the M2 macrophages can be reprogrammed into M1 macrophages that inhibit the tumor growth and proliferation. 20 Manipulation of M2 macrophages is done by interfering TAM specific signaling pathway that controls the shift between tumor-promoting and tumor-preventing macrophages. 21 There are also potential treatment possibilities that inhibit the TAM accumulation in tumor stroma and, thus, have an inhibiting influence in tumor progression.…”

Section: Macrophages and Cancermentioning

confidence: 99%

Tumor‐associated macrophages (TAMs) as biomarkers for gastric cancer: A review

Räihä

Puolakkainen

2018

Chronic Diseases and Translational Medicine

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Gastric adenocarcinoma is one of the most common types of cancer worldwide, with an incidence of a million new cases annually. In addition to having a high mortality rate due to often delayed detection and its poor response to cancer therapy, it also spreads aggressively. Inflammation has been shown to play a role in carcinogenesis. Consequently, macrophages are important in phagocytosis, antigen presenting and producing cytokines and growth factors. As a response to microenvironmental signals, they may polarize into tumor resisting M1 or tumor promoting M2 macrophages. Recently, studies have indicated that M2-type macrophage resembling tumor-associated macrophages (TAMs) might be used as an independent prognostic factor for gastric cancer. This review will discuss the possible use of TAMs as prognostic tools for gastric cancer and whether they are suitable for use in clinical environment.

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Section: Macrophages and Cancermentioning

confidence: 99%

Tumor‐associated macrophages (TAMs) as biomarkers for gastric cancer: A review

Räihä

Puolakkainen

2018

Chronic Diseases and Translational Medicine

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“…In this study, high-risk group had more abundant M1 macrophages, M0 macrophages and M2 macrophages which were found to be signi cantly associated with longer survival of GC patients. The effect of macrophage phenotypes on tumors were actually controversial, even some researchers believed that M2 Macrophages could be reprogrammed into M1 macrophages to inhibit tumor growth and proliferation through therapeutic procedures [72,73].…”

Section: Discussionmentioning

confidence: 99%

An Immune-related Gene Signature of Predicting Lymph Node Metastasis and Responses to Immune Checkpoint Inhibitor Treatment in Gastric Cancer Patients

Wang

et al. 2021

Preprint

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BackgroundImmune-related genes have been used as prognostic markers in multiple types of tumors. We aimed to develop an immune-related gene signature for predicting individual lymph node metastasis in gastric cancer (GC) patients, characterize the molecular and immune profiles of different risk patients and assess the potential value of this signature identifying patients with response to immune checkpoint inhibitor (ICI) treatment.MethodsA total of 1338 GC patients from a training dataset, three external silico validation datasets and an external clinical dataset were included in this study. The microarray analysis was used to detect differentially expressed immune-related genes (DEIGs) between lymph node metastatic and non-lymph node metastatic gastric cancer tissues. Subsequently, we built a lymph node metastasis gene signature for gastric cancer (LGSGC), and then classified patients into low-risk and high-risk groups according to the LGSGC. Moreover, we implemented association analysis for this signature and the prognosis, molecular characteristics, immune profiles and the response of ICI treatment in different risk GC patients. Resultshe receiver operating characteristics (ROC) curve analysis (an area under curve [AUC] values of 0.85) showed that the LGSGC could distinguish lymph node metastatic patients from non-lymph node metastatic patients in the training dataset. Additionally, compared to low-risk group, high-risk group exhibited worse overall survival (hazard ratio [HR]=2.42) in the training dataset. Robust diagnostic and prognostic clinical ability of the LGSGC were successfully validated in four validation datasets. Next, the high-risk patients were characterized by active cancer and immune response-related pathways, high TP53, CSMD3 and FAT4 mutation rate, high infiltration of Neutrophils, M1 Macrophages, M0 Macrophages, M2 Macrophages, T cells gamma delta and T cells follicular helper, more abundant check point, more aggressive inflammation and Type I IFN response, and more benefit from ICI. On the contrary, low-risk patients were characterized by active cancer and tumor metabolism-related pathways, low TP53 mutation rate, high infiltration of Mast cells resting, NK cells resting, Plasma cells and T cells CD4 memory resting, and less benefit from ICI therapy. Of note, we also validated the LGSGC, which identified patients having response to ICI treatment with an AUC value of 0.71 in an advanced GC dataset and an AUC value of 0.64 in an IMvigor210 dataset. ConclusionsThe LGSGC is a reliable indicator to distinguish LNM in GC and could discriminate the prognosis, molecular characteristics, immune profiles and the response of ICI treatment in different risk groups. This signature may provide a reference for treatment decisions for different risk GC patients.

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“…With respect to macrophages, it has been shown that macrophage-derived Wnt7b ligand secretion promotes breast cancer growth and metastasis through angiogenesis ( 27 ). Additional studies show that β-catenin activity in total lung macrophages influences primary lung cancer progression ( 28 , 29 ). Furthermore, β-catenin, in conjunction with an HIF-1α cofactor, has been identified as a key transcriptional regulator of AM proliferation and pathologic inflammation in the context of severe COVID-19 infection ( 30 ).…”

Section: Introductionmentioning

confidence: 99%

β-Catenin signaling in alveolar macrophages enhances lung metastasis through a TNF-dependent mechanism

Kramer¹,

Tzetzo²,

Colligan³

et al. 2023

JCI Insight

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The main cause of malignancy-related mortality is metastasis. Although metastatic progression is driven by diverse tumor-intrinsic mechanisms, there is a growing appreciation for the contribution of tumor-extrinsic elements of the tumor microenvironment, especially macrophages, which correlate with poor clinical outcomes. Macrophages consist of bone marrow–derived and tissue-resident populations. In contrast to bone marrow–derived macrophages, the transcriptional pathways that govern the pro-metastatic activities of tissue-resident macrophages (TRMs) remain less clear. Alveolar macrophages (AMs) are a TRM population with critical roles in tissue homeostasis and metastasis. Wnt/β-catenin signaling is a hallmark of cancer and has been identified as a pathologic regulator of AMs in infection. We tested the hypothesis that β-catenin expression in AMs enhances metastasis in solid tumor models. Using a genetic β-catenin gain-of-function approach, we demonstrated that (a) enhanced β-catenin in AMs heightened lung metastasis; (b) β-catenin activity in AMs drove a dysregulated inflammatory program strongly associated with Tnf expression; and (c) localized TNF-α blockade abrogated this metastatic outcome. Last, β-catenin gene CTNNB1 and TNF expression levels were positively correlated in AMs of patients with lung cancer. Overall, our findings revealed a Wnt/β-catenin/TNF-α pro-metastatic axis in AMs with potential therapeutic implications against tumors refractory to the antineoplastic actions of TNF-α.

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LSC - 2017 - Reprogramming Of Tumor Associated Macrophages By Modulating Wnt/ß-catenin Signalling In Lung Cancer

Cited by 3 publications

References 0 publications

Tumor‐associated macrophages (TAMs) as biomarkers for gastric cancer: A review

Tumor‐associated macrophages (TAMs) as biomarkers for gastric cancer: A review

An Immune-related Gene Signature of Predicting Lymph Node Metastasis and Responses to Immune Checkpoint Inhibitor Treatment in Gastric Cancer Patients

β-Catenin signaling in alveolar macrophages enhances lung metastasis through a TNF-dependent mechanism

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