Progress in the understanding of the immune microenvironment and immunotherapy in malignant pleural mesothelioma.

Progress in the understanding of the immune microenvironment and immunotherapy in malignant pleural mesothelioma. Curr Drug Targets. 2020 Jul 18;: Authors: Cheng L, Na L, Xu XL, Mao WM Abstract Malignant pleural mesothelioma (MPM) is a remarkably aggressive thoracic malignancy with a limited survival of only 5-12 months. However, MPM still remains unresponsive to conventional standards of treatment, including pleurectomy and decortication, extrapleural pneumonectomy for resectable disease with or without chemotherapy, and/or radiation therapy. The mechanism of carcinogenesis has not been fully elucidated, although approximately 80% of cases can still be linked to asbestos exposure. The tumor immune microenvironment (TME) has been proven to play an important role in MPM pathogenesis and treatment outcome. Several molecular pathways have been implicated in the MPM tumor microenvironment, such as angiogenesis, apoptosis, cell cycle regulation, and stromal processes. Immunotherapy has already shown promising results in other thoracic solid tumors, such as non-small-cell lung cancer (NSCLC). However, immunotherapy has shown less convincing results in MPM than in melanoma and NSCLC. A multicenter, randomized trial (DETERMINE) proved that immune checkpoint inhibition using tremelimumab, an anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) antibody, failed to improve median overall survival. Therefore, it is important to explore the relationship between ...
Source: Current Drug Targets - Category: Drugs & Pharmacology Authors: Tags: Curr Drug Targets Source Type: research

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CONCLUSION: Novel immunotherapies are needed in cancer patients with resistance to or relapse after current immunotherapeutic drugs. Such new treatments may include targeted agents or monoclonal antibodies to overcome the immune-suppressive tumor microenvironment. The mode of combining the novel treatments, including vaccines, needs to be matched to the patient's immune status for achieving the maximum benefit. In this scenario, specific attention should be also paid nowadays to the immune intersection between COVID-19 and cancer.PMID:34301276 | DOI:10.1186/s13046-021-02023-4
Source: Clinical Lung Cancer - Category: Cancer & Oncology Authors: Source Type: research
Although mesothelioma is the consequence of a protracted immune response to asbestos fibers and characterized by a clear immune infiltrate, novel immunotherapy approaches show less convincing results as compared to those seen in melanoma and non-small cell lung cancer. The immune suppressive microenvironment in mesothelioma is likely contributing to this therapy resistance. Therefore, it is important to explore the characteristics of the tumor microenvironment for explanations for this recalcitrant behavior. This review describes the stromal, cytokine, metabolic, and cellular milieu of mesothelioma, and attempts to make co...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Nivolumab is a fully human, immunoglobulin G4 (kappa) isotype monoclonal antibody that binds programmed cell death protein 1 (PD-1) on activated immune cells and disrupts the engagement of the receptor with its ligands programmed death-ligand 1 (PD-L1: B7-H1/CD274 and PD-L2: B7-DC/CD273), thereby abrogating inhibitory signals and augmenting the antitumor response of the host [1]. In previous clinical trials, nivolumab has shown activity in several tumor types, including melanoma, renal cell carcinoma, non-small cell lung cancer (NSCLC), hodgkin lymphoma, and malignant pleural mesothelioma.
Source: Lung Cancer - Category: Cancer & Oncology Authors: Source Type: research
AbstractBackgroundNY-ESO-1 and LAGE-1a are antigens expressed in several tumours, including non-small cell lung cancer (NSCLC). Previous clinical trials using autologous T cells directed against NY-ESO-1/LAGE-1a have shown objective responses between 40% and 60% in synovial sarcoma, metastatic melanoma and multiple myeloma. Pembrolizumab (PEM) is a monoclonal antibody that blocks PD-1/PD-L1 interaction and increases anti-tumour activity in anti-tumour T cells. Here, PEM will be used in combination with NY-ESO-1/LAGE-1a T-cell receptor engineered patient T cells (GSK3377794) to potentially improve clinical benefit in this p...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
Patients with mesothelioma are now eligible for a multicancer clinical trial studying the effectiveness of personalized immunotherapy at the University of California, San Diego Medical Center. The phase I clinical trial involves a combination of Keytruda (pembrolizumab), a proven immunotherapy drug, and an individualized vaccine based upon the genetic mutations found in each patient’s cancer. “This is the future of cancer treatment,” Dr. Ezra Cohen, principal investigator and director of the San Diego Center for Precision Immunotherapy, told The Mesothelioma Center at Asbestos.com. “Now, we still ha...
Source: Asbestos and Mesothelioma News - Category: Environmental Health Authors: Source Type: news
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
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
Cardiac tumors have generally been considered to be rare. They are often found incidentally as they tend to remain clinically silent, but they can sometimes present with symptoms secondary to obstruction, embolization, or invasion of the myocardium. Most cardiac tumors are secondary tumors from metastases, with primary cardiac tumors constituting approximately 15% of all cardiac tumors1. Although melanoma and pleural mesothelioma often have cardiac involvement, the most common cancers to be identified in cardiac metastases are lung cancer (36-39%), breast cancer (10-12%), and hematologic cancers (10-21%)2.
Source: The American Journal of Medicine - Category: General Medicine Authors: Tags: Clinical Communication to the Editor Source Type: research
Not every mesothelioma patient benefits from the immunotherapy drug Opdivo, but for the ones that do, the response can be lifesaving. Opdivo, known generically as nivolumab, continues to produce dramatic results, inching it closer to FDA approval for mesothelioma cancer. A recently published individual case report describes “an exceptional and sustained response.” Treatment with Opdivo allowed one patient to go from a downward spiral, with only weeks to live, back into the workforce. “We were blown away by the patient’s response,” lead author Riley Jones, now in his fellowship at the Universit...
Source: Asbestos and Mesothelioma News - Category: Environmental Health Authors: Source Type: news
For mesothelioma patients, immunotherapy is mostly available through clinical trials at this time. Immunotherapy is a relatively new way to treat cancer, and doctors still are learning who will respond best to these novel therapies. Newly released medical research has found men seem to respond better to immunotherapy than women. But this doesn’t mean immunotherapy is off the table for women with mesothelioma. You should learn all you can about how immunotherapy works, why it may or may not be right for you and how you can best prepare yourself if you decide an immunotherapy clinical trial is right for you. Thorough ...
Source: Asbestos and Mesothelioma News - Category: Environmental Health Authors: Source Type: news
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