Cancers, Vol. 11, Pages 714: Targeting the Interplay between Epithelial-to-Mesenchymal-Transition and the Immune System for Effective Immunotherapy

Cancers, Vol. 11, Pages 714: Targeting the Interplay between Epithelial-to-Mesenchymal-Transition and the Immune System for Effective Immunotherapy Cancers doi: 10.3390/cancers11050714 Authors: Rama Soundararajan Jared Fradette Jessica Konen Stacy Moulder Xiang Zhang Don Gibbons Navin Varadarajan Ignacio Wistuba Debasish Tripathy Chantale Bernatchez Lauren Byers Jeffrey Chang Alejandro Contreras Bora Lim Edwin Parra Emily Roarty Jing Wang Fei Yang Michelle Barton Jeffrey Rosen Sendurai Mani Over the last decade, both early diagnosis and targeted therapy have improved the survival rates of many cancer patients. Most recently, immunotherapy has revolutionized the treatment options for cancers such as melanoma. Unfortunately, a significant portion of cancers (including lung and breast cancers) do not respond to immunotherapy, and many of them develop resistance to chemotherapy. Molecular characterization of non-responsive cancers suggest that an embryonic program known as epithelial-mesenchymal transition (EMT), which is mostly latent in adults, can be activated under selective pressures, rendering these cancers resistant to chemo- and immunotherapies. EMT can also drive tumor metastases, which in turn also suppress the cancer-fighting activity of cytotoxic T cells that traffic into the tumor, causing immunotherapy to fail. In this review, we compare and contrast immunotherapy treatment options of non-small cell lung cancer (NSCLC)...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research

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Abstract Myoferlin, a protein of the ferlin family, has seven C2 domains and exhibits activity in some cells, including myoblasts and endothelial cells. Recently, myoferlin was identified as a promising target and biomarker in non-small-cell lung cancer, breast cancer, pancreatic adenocarcinoma, hepatocellular carcinoma, colon cancer, melanoma, oropharyngeal squamous cell carcinoma, head and neck squamous cell carcinoma, clear cell renal cell carcinoma and endometrioid carcinoma. This evidence indicated that myoferlin was involved in the proliferation, invasion and migration of tumour cells, the mechanism of which...
Source: J Cell Mol Med - Category: Molecular Biology Authors: Tags: J Cell Mol Med Source Type: research
Discussion MDSCs violently emerge in pathological conditions in an attempt to limit potentially harmful immune and inflammatory responses. Mechanisms supporting their expansion and survival are deeply investigated in cancer, in the perspective to reactivate specific antitumor responses and prevent their contribution to disease evolution. These findings will likely contribute to improve the targeting of MDSCs in anticancer immunotherapies, either alone or in combination with immune checkpoint inhibitors. New evidence indicates that the expansion of myeloid cell differentiation in pathology is subject to fine-tuning, as its...
Source: Frontiers in Immunology - Category: Allergy & Immunology 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
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
Conclusions MDSC are major players in the immunosuppressive scenario in cancer, thanks to their phenotype heterogeneity and critical interaction with several innate immune cells, thus representing a crucial target in oncology. Here we reviewed the interactions of MDSCs with NK cells. The contribution of key cytokines, chemokines and mediators active in this process have been discussed. We also described the contribution of MDSC on angiogenesis directly or indirectly through interactions with NK and immunosuppressive activities. A parallel of the cancer associated to the decidual counterpart of these cells is discussed, a...
Source: Frontiers in Immunology - Category: Allergy & Immunology 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
Markus Hartl* and Rainer Schneider Center of Molecular Biosciences (CMBI), Institute of Biochemistry, University of Innsbruck, Innsbruck, Austria The neuronal proteins GAP43 (neuromodulin), MARCKS, and BASP1 are highly expressed in the growth cones of nerve cells where they are involved in signal transmission and cytoskeleton organization. Although their primary structures are unrelated, these signaling proteins share several structural properties like fatty acid modification, and the presence of cationic effector domains. GAP43, MARCKS, and BASP1 bind to cell membrane phospholipids, a process reversibly regulate...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusion Although treatment with BRAF inhibitors provides rapid response in most patients, treatment resistance persists. The few clinical studies of BRAF inhibitor resistance in patients indicate that genetic alterations that activate MAPK/Erk make up half of resistance mechanisms. Preclinical studies of BRAF inhibitor resistance in melanoma support the mechanisms observed in patients and indicate that the development of resistance is more complex than single mutations. In vitro models may be very helpful in studying mechanisms in the other half of patients with no known genetic driver of BRAF inhibitor resistance. Ove...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Joe Abdo1, Christopher S. Wichman2, Nicholas E. Dietz1,3, Pawel Ciborowski4, John Fleegel1, Sumeet K. Mittal1,5 and Devendra K. Agrawal1* 1Department of Clinical and Translational Science, Creighton University School of Medicine, Omaha, NE, United States 2Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, NE, United States 3Department of Pathology, CHI Health Creighton University Medical Center, College of Medicine, Omaha, NE, United States 4Department of Pharmacology, University of Nebraska Medical Center, Omaha, NE, United States 5Norton Thoracic Institute, St....
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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