PD-L1/PD-1 axis as a potent therapeutic target in breast cancer

Publication date: Available online 16 February 2020Source: Life SciencesAuthor(s): Shima Bastaki, Mahzad Irandoust, Armin Ahmadi, Mohammad Hojjat-Farsangi, Patrick Ambrose, Shahin Hallaj, Mahdi Edalati Fathabad, Ghasem Ghalamfarsa, Gholamreza Azizi, Mehdi Yousefi, Hengameh Chalajour, Farhad Jadidi-NiaraghAbstractAlthough both the incidence and the mortality rate of breast cancer is rising, there is no potent and practical option for the treatment of these patients, particularly in advanced stages. One of the most critical challenges for treatment is the presence of complicated and extensive tumor escape mechanisms in the tumor microenvironment. Immune checkpoint molecules are of the main immunosuppressive mechanisms used by cancerous cells to block anti-cancer immune responses. Among these molecules, PD-1 (Programmed cell death) and PD-L1 (programmed cell death-ligand 1) have been considered as worthy therapeutic targets for breast cancer therapy. In this review, we intend to discuss the immunobiology and signaling of the PD-1/PD-L1 axis and highlight its importance as a worthy therapeutic target in breast cancer. We believe that the prognostic value of PD-L1 depends on the breast cancer subtype. Moreover, the combination of PD-1/PD-L1 targeting with immune-stimulating vaccines can be considered as an effective therapeutic strategy in breast cancer.
Source: Life Sciences - Category: Biology Source Type: research

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Publication date: Available online 13 March 2020Source: Life SciencesAuthor(s): Balamurugan Shanmugaraj, Lohanathan Bharathi Priya, B. Mahalakshmi, Shanmugam Subbiah, Rouh-Mei Hu, Bharath Kumar Velmurugan, Rathinasamy Baskaran
Source: Life Sciences - Category: Biology Source Type: research
AbstractClinical progress in the field of HER2-positive breast cancer therapy has been dramatically improved by understanding of the immune regulatory mechanisms of tumor microenvironment. Passive immunotherapy utilizing recombinant monoclonal antibodies (mAbs), particularly trastuzumab and pertuzumab has proved to be an effective strategy in HER2-positive breast cancer treatment. However, resistance to mAb therapy and relapse of disease are still considered important challenges in clinical practice. There are increasing reports on the induction of cellular and humoral immune responses in HER2-positive breast cancer patien...
Source: Archivum Immunologiae et Therapiae Experimentalis - Category: Allergy & Immunology Source Type: research
Abstract Immuno-biotechnology is one of the fastest growing areas in the field of biotechnology. Digital World Biology's Biotech-Careers.org database of biotechnology employers (>6800) has nearly 700 organizations that are involved with immunology in some way. With the advent of next generation DNA sequencing, and other technologies, immuno-biotechnology has significantly increased the use of computing technologies to decipher the meaning of large datasets and predict interactions between immune receptors (antibodies / T-Cell receptors / MHC) and their targets. The use of new technologies like immune-profiling ...
Source: Journal of Biomolecular Techniques : JBT - Category: Molecular Biology Authors: Tags: J Biomol Tech Source Type: research
Authors: Godoy-Calderón MJ, González-Marcano E, Carballo J, Convit AF Abstract Breast cancer therapies using checkpoints alone have not been highly effective. Based on previous experiences using the ConvitVax, an autologous tumor cells/bacillus Calmette-Guérin (BCG)/formalin-based vaccine, in breast cancer and the potential success of combined therapies, we sought to ascertain whether the ConvitVax combined with anti-PD-1 enhances the antitumor effect in a 4T1 breast cancer model. Animals received four weekly injections of either PBS (G1), ConvitVax (200 μg cell homogenate, 0.0625 mg BCG, 0....
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
The 2019 Lasker medical and research awards celebrate advances in scientists’ understanding of T and B cells, Herceptin antibodies for treating breast cancer, and vaccine coverage around the...
Source: The Scientist - Category: Science Tags: News & Opinion Source Type: news
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
Conclusion Several TISC-based immunotherapeutic approaches are under development in various stages of preclinical studies. As outlined in this review article, a careful and more exhaustive genetic and metabolic understanding of TISC-associated phenotypes is critical to develop novel TISC based immunotherapies. Various components within the tumor microenvironment such as tumor cells, infiltrating immune cells, and supporting stromal cells impact the TISC metabolism. This unique metabolic profile leads to upregulation of certain enzymes and proteins such as ALDH1, CEP55, IDO COA1 etc., which can be utilized for development ...
Source: Frontiers in Oncology - Category: Cancer & Oncology 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
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