Immune checkpoint combinations from mouse to man

Abstract The discovery that antibody blockade of the T cell co-inhibitory receptor cytotoxic T lymphocyte-associated protein 4 (CTLA-4) can restore tumor immunity against many murine transplantable tumors leading to complete rejection of established cancer forever changed the field of immunotherapy. In more robust murine models as well as human cancer, however, CTLA-4 blockade alone can slow tumor growth and extend patient survival, but is rarely curative. Subsequent studies have revealed a large family of T cell immune checkpoint receptors which tumors engage to shield themselves from host immunity. As with CTLA-4, blockade of one of these additional inhibitory receptors, programmed death 1, has led to remarkable therapeutic responses against tumors of multiple lineages. Checkpoint monotherapy has demonstrated that durable, immune-mediated cures of established metastatic cancers are possible, yet the percentage of patients experiencing these outcomes remains low due to both redundant mechanisms of immune suppression in the tumor and limiting toxicity associated with some therapies. Thus, extending the curative potential of immunotherapy to a larger percentage of patients with a broader spectrum of malignancies will likely require combinations of co-inhibitory blockade and co-stimulatory activation designed to peel back multiple layers of tumor immune suppression while at the same time minimizing immune-mediated toxicity. As over a dozen T cell immune checkpoints and...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research

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Pancreatic cancer is considered a lethal disease with a low survival rate due to its late-stage diagnosis, few opportunities for resection and lack of effective therapeutic strategies. Multiple, highly complex effects of gut microbiota on pancreatic cancer have been recognized as potential strategies for targeting tumorigenesis, development and treatment in recent decades; some of the treatments include antibiotics, probiotics, and fecal microbiota transplantation. Several bacterial species are associated with carcinogenesis of the pancreas, while some bacterial metabolites contribute to tumor-associated low-grade inflamma...
Source: Frontiers in cellular and infection microbiology - Category: Microbiology Source Type: research
amouzis Schizas Hepatocellular carcinoma (HCC) is one of one of the most frequent liver cancers and the fourth leading cause of cancer-related mortality worldwide. Current treatment options such as surgery, neoadjuvant chemoradiotherapy, liver transplantation, and radiofrequency ablation will benefit only a very small percentage of patients. Immunotherapy is a novel treatment approach representing an effective and promising option against several types of cancer. The aim of our study is to present the currently ongoing clinical trials and to evaluate the efficacy of immunotherapy in HCC. In this paper, we demonstrat...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
A lymphocyte of the innate immune response, Natural Killer (NK) cells are phenotypically defined by the absence of CD3 and the presence of CD56 on their surface.1, 2 Functionally, they resemble CD8+ cytotoxic T cells.3 NK cells derive their name from their ability to spontaneously kill their targets without the need for a prior encounter of the antigen, as they have readily available lytic granules that can activate within minutes,4 unlike their T cell counterparts. NK cell targets include stressed, virally-infected, and transformed cells.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
A lymphocyte of the innate immune response, Natural Killer (NK) cells are phenotypically defined by the absence of CD3 and the presence of CD56 on their surface.1, 2 Functionally, they resemble CD8+ cytotoxic T cells.3 NK cells derive their name from their ability to spontaneously kill their targets without the need for a prior encounter of the antigen, as they have readily available lytic granules that can activate within minutes,4 unlike their T cell counterparts. NK cell targets include stressed, virally-infected, and transformed cells.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
The objective of this review is to discuss the benefit and the limits of pediatric therapeutic strategies in adults and the perspectives offered by new approaches including immunotherapies. PMID: 32981690 [PubMed - as supplied by publisher]
Source: Bulletin du Cancer - Category: Cancer & Oncology Authors: Tags: Bull Cancer Source Type: research
Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Hepatocellular carcinoma is a highly prevalent and lethal cancer that many therapeutics are being tested for this disease. It has the potential to be a highly immune-responsive tumor given its inflammatory origins. The first immunotherapies were anti-programmed death-1 monotherapies, which improved response rates and survival. Novel immunotherapy combinations and immunotherapy show promise in frontline treatment. The novel antibody therapy combination of atezolizumab and bevacizumab may be practice changing. Although these landmark studies seem to offer new treatment options, the role of immunotherapy in the liver transpla...
Source: Clinics in Liver Disease - Category: Gastroenterology Authors: Source Type: research
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
In this study, we found that an angiogenesis inhibitor apatinib enhanced anti-PD-1 therapy for colon cancer in mice via promoting PD-L1 expression. Apatinib treatment upregulated PD-L1 expression in various colon cancer cells both at the mRNA and protein levels. Further, apatinib-treated cancer cells hampered activation and IFN-γ secretion of T cells in the co-culture system, which was reversed by the anti-PD-1 antibody. Based on this, the combination of apatinib with anti-PD-1 on colon cancer growth in mice was examined. The combination treatment showed more significant inhibition on the growth of transplanted tumor...
Source: International Immunopharmacology - Category: Allergy & Immunology Authors: Tags: Int Immunopharmacol Source Type: research
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Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
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