ST2 Signaling in the Tumor Microenvironment.

ST2 Signaling in the Tumor Microenvironment. Adv Exp Med Biol. 2020;1240:83-93 Authors: Chang CP, Hu MH, Hsiao YP, Wang YC Abstract Suppression of tumorigenicity 2 (ST2), also known as interleukin-1 receptor-like 1 (IL1RL1), is one of the natural receptors of IL-33. Three major isoforms, ST2L (transmembrane form), sST2 (soluble form), and ST2V, are generated by alternative splicing. Damage to stromal cells induces necrosis and release of IL-33, which binds to heterodimeric ST2L/IL-1RAcP complex on the membrane of a variety of immune cells. This IL-33/ST2L signal induces transcription of the downstream inflammatory and anti-inflammatory genes by activating diverse intracellular kinases and factors to mount an adequate immune response, even in tumor microenvironment. For example, activation of IL-33/ST2L signal may trigger Th2-dependent M2 macrophage polarization to facilitate tumor progression. Notably, sST2 is a soluble form of ST2 that lacks a transmembrane domain but preserves an extracellular domain similar to ST2L, which acts as a "decoy" receptor for IL-33. sST2 has been shown to involve in the inflammatory tumor microenvironment and the progression of colorectal cancer, non-small cell lung cancer, and gastric cancer. Therefore, targeting the IL-33/ST2 axis becomes a promising new immunotherapy for treatment of many cancers. This chapter reviews the recent findings on IL-33/ST2L signaling in tumor microenvironment, the trafficking mode of s...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research

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Conclusion MTDH is pro-oncogenic factor playing multifaceted and diverse roles in cancer progression. Its association and central role in regulating signaling pathways such a MAPK, wnt/β-catenin, PI3K/AkT, NF-κβ pathways in various cancers shows that it plays a vital role in metastasis. MTDH contribution to chemo and radiotherapy resistance provides a new direction for the development of anticancer therapeutics. Multiple mechanisms converge to promote expression of MTDH in cancers. Further studies are therefore warranted to determine whether the elevated MTDH expression has prognostic value for development...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Michal Yalon1†, Amos Toren1,2†, Dina Jabarin2, Edna Fadida3, Shlomi Constantini3 and Ruty Mehrian-Shai1* 1Pediatric Hemato-Oncology, Edmond and Lilly Safra Children's Hospital and Cancer Research Center, Sheba Medical Center, Ramat Gan, Israel 2The Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel 3Department of Pediatric Neurosurgery, Dana Children's Hospital, Tel-Aviv-Sourasky Medical Center, Tel Aviv, Israel Pediatric brain tumors are the most common solid tumor type and the leading cause of cancer-related death in children. The immune system plays an important r...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusions This review describes how leukocyte-heparanase can be a double-edged sword in tumor progression; it can enhance tumor immune surveillance and tumor cell clearance, but also promote tumor survival and growth. We also discuss the potential of using heparanase in leukocyte therapies against tumors, and the effects of heparanase inhibitors on tumor progression and immunity. We are just beginning to understand the influence of heparanase on a pro/anti-tumor immune response, and there are still many questions to answer. How do the pro/anti-tumorigenic effects of heparanase differ across different cancer types? Does...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusions and Future Perspectives It is now evident that NK/ILC family plays a pivotal role in the immune defenses. Recent studies in murine and human settings demonstrated that the expression of several inhibitory checkpoints, that may be detrimental in the tumor context, is not restricted to T lymphocytes, revealing an important, yet poorly appreciated, contribution of their expression on innate immune cells. Thus, in the recent years different immunotherapy approaches, based on the blockade of inhibitory NK cell receptors, have been developed in order to unleash NK cell cytotoxicity. This is particularly important in...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
This study aimed to investigate whether combining anti-PD-L1 Atezolizumab with BEV may have a synergistic effect and enhance the efficacy of both treatments in cisplatin resistant epithelial ovarian cancer (CREOC). We retrospectively analyzed 124 epithelial ovarian cancer (EOC) patients from Gynecologic Oncology Department of Tianjin Cancer Hospital between January 2013 and June 2018, who all were diagnosed with cisplatin resistance due to progressing
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Eleonora A. Braga1*†, Marina V. Fridman2†, Vitaly I. Loginov1,3, Alexey A. Dmitriev4 and Sergey G. Morozov1 1Institute of General Pathology and Pathophysiology, Moscow, Russia 2Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia 3Research Center of Medical Genetics, Moscow, Russia 4Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia Clear cell renal cell carcinoma (ccRCC) is the third most common urological cancer, and it has the highest mortality rate. The increasing drug resistance of metastatic ccRCC has resulted in the search f...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
In this study, the gut microbiota of 30 LC patients and 30 healthy controls were examined via next-generation sequencing of 16S rRNA and analyzed for diversity and biomarkers. We found that there was no decrease in significant microbial diversity (alpha diversity) in LC patients compared to controls (P observed = 0.1422), while the composition (beta diversity) differed significantly between patients and controls (phylum [stress = 0.153], class [stress = 0.16], order [stress = 0.146], family [stress = 0.153]). Controls had a higher abundance of the bacterial phylum Actinobacteria and genus Bifidobacterium, while patients wi...
Source: Frontiers in cellular and infection microbiology - Category: Microbiology Source Type: research
In this study, we evaluated whether the combination of focused ultrasound (FUS) and microbubbles can improve adoptively NK-92MI cell infiltration into ovarian tumors through biodistribution, immunofluorescence, and flow cytometry. The treatment effects of using this strategy twice a week were explored. The potential molecular mechanism of FUS assisting NK cell therapy was also initially explored through evaluating the expression of ICAM1 and CX3CL1 by qRT-PCR. Our results indicated that FUS and microbubbles can improve NK-92MI cells’ infiltration into tumors, and the combination of FUS and NK-92MI cells had a better ...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusions and Perspectives In this review, we have discussed important milestones from the early description of “Serum-sickness” as being due to antibodies directed against Neu5Gc epitopes all the way to the present-day therapeutic implications of these antibodies in cancer therapy. Some of these milestones have been represented in a concise timeline (Figure 6). While the “Xenosialitis” hypothesis is well-supported in the human-like mouse models, it has yet to be conclusively proven in humans. It remains to be seen if “Xenosialitis” plays a role in other uniquely-human diseases. FI...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
This study was supported by the Shanghai Sailing Program [grant number 17YF1425200, 2017]; Chinese National Natural Science Funding [grant number 81702249, 2017]; Science and Technology Commission of Shanghai Municipality [grant number 17511103403, 2017]; The funder has no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Conflict of Interest Statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Acknowledgments We acknowledge the ex...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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