Search results for "immune checkpoint"
showing 10 items of 130 documents
Abstract 1847: Anti-GARP antibody DS-1055a augments antitumor immunity by depleting highly suppressive GARP+ regulatory T cells
2021
Abstract Immune checkpoint blockers (ICBs) have drastically changed the clinical care of cancer; however, the population of patients who can benefit is relatively small because of intrinsic or acquired resistance to immune therapy. To evade immune destruction, tumors exploit several distinct strategies including immunosuppressive cells such as regulatory T (Treg) cells. Treg cells, an essential component for maintaining self-tolerance, inhibit antitumor immunity, consequently hindering protective cancer immunosurveillance and hampering effective antitumor immune responses in tumor-bearing hosts. It is often reported that a high ratio of Treg cells to effector CD8+ T cells is associated with…
Abstract B290: Activation of the PD-1 pathway contributes to immune escape in EGFR-driven lung tumors.
2013
Abstract The recent clinical success of therapeutic blockade of the immune checkpoint Programmed Death (PD)-1 in advanced lung cancer patients suggests that mechanisms of immune escape may contribute to lung tumor pathogenesis. We identified a correlation between Epidermal Growth Factor Receptor (EGFR) pathway activation and a gene signature indicative of immunosuppression manifested by upregulation of PD-1, PD-L1, cytotoxic T lymphocyte antigen-4 (CTLA-4) and multiple tumor-promoting inflammatory cytokines. Accordingly, we identified a decrease in the number of cytotoxic T cells and an increase in markers of T cell exhaustion in genetically engineered mouse models (GEMMs) of EGFR-driven lu…
A shared tumor-antigen RNA-lipoplex vaccine with/without anti-PD1 in patients with checkpoint-inhibition experienced melanoma.
2020
3136 Background: Cancer vaccines are considered unsuitable for patients with advanced tumours and have not been clinically successful. Methods: Lipo-MERIT is an ongoing phase 1/2 trial (NCT02410733) with melanoma FixVac, a liposomal RNA vaccine targeting four non-mutant shared tumour-associated antigens (TAAs) (MAGE-A3, NY-ESO-1, tyrosinase, TPTE). Patients with stage IIIB-C and IV melanoma are eligible. The trial comprises 7 dose escalation and 3 dose expansion cohorts, the latter with FixVac alone or combined with anti-PD1. Eight doses of FixVac are administered i.v. weekly/bi-weekly followed by optional continued monthly treatment. This abstract summarizes the findings of an exploratory…
The Role of Immune Checkpoint Blockade in the Hepatocellular Carcinoma: A Review of Clinical Trials.
2021
The prevalence of primary liver cancer is rapidly rising all around the world. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Unfortunately, the traditional treatment methods to cure HCC showed poor efficacy in patients who are not candidates for liver transplantation. Until recently, tyrosine kinase inhibitors (TKIs) were the front-line treatment for unresectable liver cancer. However, rapidly emerging new data has drastically changed the landscape of HCC treatment. The combination treatment of atezolizumab plus bevacizumab (immunotherapy plus anti-VEGF) was shown to provide superior outcomes and has become the new standard first-line treatment for unresect…
Exploring the Dynamic Crosstalk between the Immune System and Genetics in Gastrointestinal Stromal Tumors
2022
Gastrointestinal Stromal Tumors (GISTs) represent a paradigmatic model of oncogene addiction. Despite the well-known impact of the mutational status on clinical outcomes, we need to expand our knowledge to other factors that influence behavior heterogeneity in GIST patients. A growing body of studies has revealed that the tumor microenvironment (TME), mostly populated by tumor-associated macrophages (TAMs) and lymphocytes (TILs), and stromal differentiation (SD) have a significant impact on prognosis and response to treatment. Interestingly, even though the current knowledge of the role of immune response in this setting is still limited, recent pre-clinical and clinical data have highlight…
Immune checkpoint inhibitors-associated pericardial disease: a systematic review of case reports
2021
Treatment with immune checkpoint inhibitors (ICIs) can be complicated by cardiovascular toxicity, including pericardial disease. To date, no prospective studies specifically investigated the optimal treatment of ICI-associated pericardial disease, and the available evidence is based on case reports and series only. We performed a systematic review of case reports and series including 20 publications for a total of 28 cases of ICI-associated pericardial disease. In this review, pericardial disease was reversible in the majority of cases (75%), although 2 deaths were reported. The majority of cases were life-threatening (G4, 53.6%) or severe (G3, 21.4%), requiring pericardiocentesis. Higher r…
Novel Approaches for Glioblastoma Treatment: Focus on Tumor Heterogeneity, Treatment Resistance, and Computational Tools
2019
BACKGROUND: Glioblastoma (GBM) is a highly aggressive primary brain tumor. Currently, the suggested line of action is the surgical resection followed by radiotherapy and treatment with the adjuvant temozolomide (TMZ), a DNA alkylating agent. However, the ability of tumor cells to deeply infiltrate the surrounding tissue makes complete resection quite impossible, and in consequence, the probability of tumor recurrence is high, and the prognosis is not positive. GBM is highly heterogeneous and adapts to treatment in most individuals. Nevertheless, these mechanisms of adaption are unknown. RECENT FINDINGS: In this review, we will discuss the recent discoveries in molecular and cellular heterog…
Combining immunotherapy and anticancer agents: the right path to achieve cancer cure?
2015
Recent clinical trials revealed the impressive efficacy of immunological checkpoint blockade in different types of metastatic cancers. Such data underscore that immunotherapy is one of the most promising strategies for cancer treatment. In addition, preclinical studies provide evidence that some cytotoxic drugs have the ability to stimulate the immune system, resulting in anti-tumor immune responses that contribute to clinical efficacy of these agents. These observations raise the hypothesis that the next step for cancer treatment is the combination of cytotoxic agents and immunotherapies. The present review aims to summarize the immune-mediated effects of chemotherapeutic agents and their …
Immunotherapy With Human Gamma Delta T Cells—Synergistic Potential of Epigenetic Drugs?
2018
Epigenetics has emerged as one of the fastest growing concepts, adding more than 45 new publications every day, spreading through various fields ( 1). Conrad Waddington coined the term “epigenetics” in 1942; however, a multitude of definitions has been endorsed by different researchers. In essence, Waddington’s definition of “epigenetics” and its redefinition by Holiday is at the heart of cellular function. Hence, it is obvious that epigenetic regulation plays a central role also in the specification, differentiation, and functional plasticity of T lymphocytes ( 2). T-cell fate decision in progenitor cells, functional CD4 T-cell plasticity, CD8 T-cell differentiation, but also T-cell memory…
Immunotherapy in gastrointestinal cancer: Recent results, current studies and future perspectives
2016
The new therapeutic approach of using immune checkpoint inhibitors as anticancer agents is a landmark innovation. Early studies suggest that immune checkpoint inhibition might also be effective in patients with gastrointestinal cancer. To improve the efficacy of immunotherapy, different strategies are currently under evaluation. This review summarises the discussion during the European Organisation for Research and Treatment of Cancer Gastrointestinal Tract Cancer Translational Research Meeting in Mainz in November 2014 and provides an update on the most recent results of immune therapy in gastrointestinal cancers. Knowledge of potential relationships between tumour cells and their microenv…