scholarly journals Comment on “Tumor-initiating cells establish an IL-33–TGF-β niche signaling loop to promote cancer progression”

Science ◽  
2021 ◽  
Vol 372 (6538) ◽  
pp. eabf2022
Author(s):  
Jasper B. J. Kamphuis ◽  
William P. M. Worrall ◽  
Julien Stackowicz ◽  
Aurélie Mougel ◽  
Emilie Mauré ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Immunoglobulin E ◽  
Research Articles ◽  
Tumor Initiating Cells ◽  
Tumor Associated Macrophages ◽  
Interleukin 33

Taniguchi et al. (Research Articles, 17 July 2020, p. 269) claim that the cytokine interleukin-33 induces accumulation of tumor-associated macrophages expressing the immunoglobulin E receptor FcεRI. Although these findings hold great therapeutic promise, we provide evidence that the anti-FcεRI antibody used in this study is not specific for FcεRI on macrophages, which raises concerns about the validity of some of the conclusions.

Tumor-initiating cells establish an IL-33–TGF-β niche signaling loop to promote cancer progression

Science ◽  
2020 ◽  
Vol 369 (6501) ◽  
pp. eaay1813 ◽  
Author(s):  
Sachiko Taniguchi ◽  
Ajit Elhance ◽  
Avery Van Duzer ◽  
Sushil Kumar ◽  
Justin J. Leitenberger ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Transforming Growth Factor ◽  
Immunoglobulin E ◽  
Transforming Growth Factor Β ◽  
Drug Resistant ◽  
Tumor Initiating Cells ◽  
Interleukin 33 ◽  
High Affinity ◽  
Feedforward Loop ◽  
Close Proximity

Targeting the cross-talk between tumor-initiating cells (TICs) and the niche microenvironment is an attractive avenue for cancer therapy. We show here, using a mouse model of squamous cell carcinoma, that TICs play a crucial role in creating a niche microenvironment that is required for tumor progression and drug resistance. Antioxidant activity in TICs, mediated by the transcription factor NRF2, facilitates the release of a nuclear cytokine, interleukin-33 (IL-33). This cytokine promotes differentiation of macrophages that express the high-affinity immunoglobulin E receptor FcεRIα and are in close proximity to TICs. In turn, these IL-33–responding FcεRIα+ macrophages send paracrine transforming growth factor β (TGF-β) signals to TICs, inducing invasive and drug-resistant properties and further upregulating IL-33 expression. This TIC-driven, IL-33–TGF-β feedforward loop could potentially be exploited for cancer treatment.

scholarly journals Response to Comment on “Tumor-initiating cells establish an IL-33–TGF-β niche signaling loop to promote cancer progression”

Science ◽  
2021 ◽  
Vol 372 (6538) ◽  
pp. eabf3316
Author(s):  
Sachiko Taniguchi ◽  
Ajit Elhance ◽  
Avery Van Duzer ◽  
Sushil Kumar ◽  
Justin Leitenberger ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cell ◽  
Cancer Progression ◽  
Squamous Cell ◽  
Immunoglobulin E ◽  
Marrow Cell ◽  
Squamous Cell Carcinomas ◽  
Nonspecific Binding ◽  
Tumor Initiating Cells ◽  
High Affinity

Kamphuis et al. argue that macrophages accumulated in the proximity of tumor-initiating cells do not express the high-affinity immunoglobulin E receptor FcεRIα. Although we cannot exclude the possibility of nonspecific binding of anti-FcεRIα antibody (clone MAR-1), we provide evidence that macrophages in squamous cell carcinomas express FcεRIα and that IL-33 induces FcεRIα expression in bone marrow cell–derived macrophages.

scholarly journals Iron-Bound Lipocalin-2 from Tumor-Associated Macrophages Drives Breast Cancer Progression Independent of Ferroportin

Metabolites ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 180
Author(s):  
Christina Mertens ◽  
Matthias Schnetz ◽  
Claudia Rehwald ◽  
Stephan Grein ◽  
Eiman Elwakeel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Progression ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Lung Metastases ◽  
Expression Profiles ◽  
The Cancer Genome Atlas ◽  
Lipocalin 2 ◽  
Tumor Associated Macrophages

Macrophages supply iron to the breast tumor microenvironment by enforced secretion of lipocalin-2 (Lcn-2)-bound iron as well as the increased expression of the iron exporter ferroportin (FPN). We aimed at identifying the contribution of each pathway in supplying iron for the growing tumor, thereby fostering tumor progression. Analyzing the expression profiles of Lcn-2 and FPN using the spontaneous polyoma-middle-T oncogene (PyMT) breast cancer model as well as mining publicly available TCGA (The Cancer Genome Atlas) and GEO Series(GSE) datasets from the Gene Expression Omnibus database (GEO), we found no association between tumor parameters and Lcn-2 or FPN. However, stromal/macrophage-expression of Lcn-2 correlated with tumor onset, lung metastases, and recurrence, whereas FPN did not. While the total iron amount in wildtype and Lcn-2−/− PyMT tumors showed no difference, we observed that tumor-associated macrophages from Lcn-2−/− compared to wildtype tumors stored more iron. In contrast, Lcn-2−/− tumor cells accumulated less iron than their wildtype counterparts, translating into a low migratory and proliferative capacity of Lcn-2−/− tumor cells in a 3D tumor spheroid model in vitro. Our data suggest a pivotal role of Lcn-2 in tumor iron-management, affecting tumor growth. This study underscores the role of iron for tumor progression and the need for a better understanding of iron-targeted therapy approaches.

scholarly journals Interleukin-33-Enhanced CXCR4 Signaling Circuit Mediated by Carcinoma-Associated Fibroblasts Promotes Invasiveness of Head and Neck Cancer

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3442
Author(s):  
Yu-Chun Lin ◽  
Wen-Yen Huang ◽  
Tsai-Yu Lee ◽  
Yi-Ming Chang ◽  
Su-Feng Chen ◽  
...  
Keyword(s):  
Head And Neck ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Disease Free Survival ◽  
Interleukin 33 ◽  
Cxcr4 Signaling ◽  
Regulatory Circuit ◽  
Carcinoma Associated Fibroblasts ◽  
Self Production

Despite recent advances, treatment for head and neck squamous cell carcinoma (HNSCC) has limited efficacy in preventing tumor progression. We confirmed previously that carcinoma-associated fibroblasts (CAF)-induced interleukin-33 (IL-33) contributed to cancer progression. However, the molecular mechanisms underlying the complex communication network of the tumor microenvironment merited further evaluation. To simulate the IL-33-induced autocrine signaling, stable clones of IL-33-overexpressing HNSCC cells were established. Besides well-established IL-33/ST2 and SDF1/CXCR4 (stromal-derived factor 1/C-X-C motif chemokine receptor 4) signaling, the CAF-induced IL-33 upregulated CXCR4 via cancer cell induction of IL-33 self-production. The IL-33-enhanced-CXCR4 regulatory circuit involves SDF1/CXCR4 signaling activation and modulates tumor behavior. An in vivo study confirmed the functional role of IL-33/CXCR4 in tumor initiation and metastasis. The CXCR4 and/or IL-33 blockade reduced HNSCC cell aggressiveness, with attenuated invasions and metastases. Immunohistochemistry confirmed that IL-33 and CXCR4 expression correlated significantly with disease-free survival and IL-33-CXCR4 co-expression predicted a poor outcome. Besides paracrine signaling, the CAF-induced IL-33 reciprocally enhanced the autocrine cancer-cell self-production of IL-33 and the corresponding CXCR4 upregulation, leading to the activation of SDF1/CXCR4 signaling subsequent to cancer progression. Thus, targeting the IL-33-enhanced-CXCR4 regulatory circuit attenuates tumor aggressiveness and provides a potential therapeutic option for improving the prognosis in HNSCC patients.

scholarly journals Antitumor effect of Batf2 through IL-12 p40 up-regulation in tumor-associated macrophages

2017 ◽  
Vol 114 (35) ◽  
pp. E7331-E7340 ◽  
Author(s):  
Hisashi Kanemaru ◽  
Fumihiro Yamane ◽  
Kiyoharu Fukushima ◽  
Takanori Matsuki ◽  
Takahiro Kawasaki ◽  
...  
Keyword(s):  
T Cells ◽  
Cancer Progression ◽  
T Cell Activation ◽  
Cell Activation ◽  
Antitumor Effect ◽  
Leucine Zipper ◽  
Cancer Prognosis ◽  
Tumor Associated Macrophages ◽  
Basic Leucine Zipper

The development of effective treatments against cancers is urgently needed, and the accumulation of CD8+ T cells within tumors is especially important for cancer prognosis. Although their mechanisms are still largely unknown, growing evidence has indicated that innate immune cells have important effects on cancer progression through the production of various cytokines. Here, we found that basic leucine zipper transcription factor ATF-like 2 (Batf2) has an antitumor effect. An s.c. inoculated tumor model produced fewer IL-12 p40+ macrophages and activated CD8+ T cells within the tumors of Batf2−/− mice compared with WT mice. In vitro studies also revealed that the IL-12 p40 expression was significantly lower in Batf2−/− macrophages following their stimulation by toll-like receptor ligands, such as R848. Additionally, we found that BATF2 interacts with p50/p65 and promotes IL-12 p40 expression. In conclusion, Batf2 has an antitumor effect through the up-regulation of IL-12 p40 in tumor-associated macrophages, which eventually induces CD8+ T-cell activation and accumulation within the tumor.

scholarly journals Bimodal CD40/Fas-Dependent Crosstalk between iNKT Cells and Tumor-Associated Macrophages Impairs Prostate Cancer Progression

Cell Reports ◽  
2018 ◽  
Vol 22 (11) ◽  
pp. 3006-3020 ◽  
Author(s):  
Filippo Cortesi ◽  
Gloria Delfanti ◽  
Andrea Grilli ◽  
Arianna Calcinotto ◽  
Francesca Gorini ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Prostate Cancer Progression ◽  
Inkt Cells ◽  
Tumor Associated Macrophages

scholarly journals Non-Coding RNAs in Lung Tumor Initiation and Progression

2020 ◽  
Vol 21 (8) ◽  
pp. 2774 ◽  
Author(s):  
Ruben Mercado Santos ◽  
Cerena Moreno ◽  
Wen Cai Zhang
Keyword(s):  
Lung Cancer ◽  
Cancer Progression ◽  
Tumor Suppressors ◽  
Lung Tumor ◽  
Circular Rnas ◽  
Tumor Initiating Cells ◽  
Cancer Initiation ◽  
Non Coding Rnas ◽  
Society Today ◽  
Cell Signaling Pathways

Lung cancer is one of the deadliest forms of cancer affecting society today. Non-coding RNAs, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), through the transcriptional, post-transcriptional, and epigenetic changes they impose, have been found to be dysregulated to affect lung cancer tumorigenesis and metastasis. This review will briefly summarize hallmarks involved in lung cancer initiation and progression. For initiation, these hallmarks include tumor initiating cells, immortalization, activation of oncogenes and inactivation of tumor suppressors. Hallmarks involved in lung cancer progression include metastasis and drug tolerance and resistance. The targeting of these hallmarks with non-coding RNAs can affect vital metabolic and cell signaling pathways, which as a result can potentially have a role in cancerous and pathological processes. By further understanding non-coding RNAs, researchers can work towards diagnoses and treatments to improve early detection and clinical response.

scholarly journals Arming Tumor-Associated Macrophages to Reverse Epithelial Cancer Progression

2019 ◽  
Vol 79 (19) ◽  
pp. 5048-5059 ◽  
Author(s):  
Hiromi I. Wettersten ◽  
Sara M. Weis ◽  
Paulina Pathria ◽  
Tami Von Schalscha ◽  
Toshiyuki Minami ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Epithelial Cancer ◽  
Tumor Associated Macrophages

scholarly journals Effect of Dietary Omega-3 Fatty Acids on Tumor-Associated Macrophages and Prostate Cancer Progression

The Prostate ◽  
2016 ◽  
Vol 76 (14) ◽  
pp. 1293-1302 ◽  
Author(s):  
Pei Liang ◽  
Susanne M. Henning ◽  
Shiruyeh Schokrpur ◽  
Lily Wu ◽  
Ngan Doan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Fatty Acids ◽  
Cancer Progression ◽  
Omega 3 Fatty Acids ◽  
Prostate Cancer Progression ◽  
Omega 3 ◽  
Tumor Associated Macrophages
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