Search results for "Immune checkpoints"
showing 10 items of 11 documents
Targeting Immune Modulators in Glioma While Avoiding Autoimmune Conditions
2021
Simple Summary Glioblastoma multiforme is a futile disease usually leading to the patient’s death within one year post-diagnosis; therefore, novel treatment options are desperately needed. In this regard, activation of the inert immune system has moved into focus in recent years. Malignant brain tumors, as well as autoimmune diseases, elicit aberrant immune responses. In this way, glioma escapes the host’s immune system and, thus, activation of the immune response in order to reduce tumor tolerance can serve as an alternative treatment option. Immune checkpoint modulators in combination with traditional therapies have gained attention in both glioma and autoimmune diseases. In this review, …
Immune checkpoint inhibitors in lung cancer: the holy grail has not yet been found…
2017
Lung cancer is rich in molecular complexities and driven by different abnormal molecular pathways. Personalised medicine has begun to bring new hope for the treatment of patients with lung cancer, especially non-small cell lung cancer (NSCLC). The development of molecularly targeted therapy (small molecules and monoclonal antibodies) has significantly improved outcomes in the metastatic setting for patients with NSCLC whose tumours harbour activated oncogenes such as epidermal growth factor receptor (EGFR) and translocated genes like anaplastic lymphoma kinase (ALK). In addition, immune checkpoint inhibitors have also dramatically changed the therapeutic landscape of NSCLC. In particular, m…
Baseline plasma levels of soluble PD-1, PD-L1, and BTN3A1 predict response to nivolumab treatment in patients with metastatic renal cell carcinoma: a…
2020
Despite a proportion of renal cancer patients can experiment marked and durable responses to immune-checkpoint inhibitors, the treatment efficacy is widely variable and identifying the patient who will benefit from immunotherapy remains an issue. We performed a prospective study to investigate if soluble forms of the immune-checkpoints PD-1 (sPD-1), PD-L1 (sPD-L1), pan-BTN3As, BTN3A1, and BTN2A1, could be candidate to predict the response to immune-checkpoint blockade therapy. We evaluated the plasma levels in a learning cohort of metastatic clear cell renal carcinoma (mccRCC) patients treated with the anti-PD-1 agent nivolumab by ad hoc developed ELISA’s. Using specific cut-offs determined…
Innovative therapy, monoclonal antibodies, and beyond: Highlights from the eighth annual meeting
2018
The eighth annual conference of “Innovative therapy, monoclonal antibodies, and beyond” was held in Milan on Jan. 26, 2018, and hosted by Fondazione IRCCS–Istituto Nazionale dei Tumori (Fondazione IRCCS INT). The conference was divided into two main scientific sessions, of i) pre-clinical assays and novel biotargets, and ii) clinical translation, as well as a third session of presentations from young investigators, which focused on recent achievements within Fondazione IRCCS INT on immunotherapy and targeted therapies. Presentations in the first session addressed the issue of cancer immunotherapy activity with respect to tumor heterogeneity, with key topics addressing: 1) tumor heterogeneit…
Vγ9Vδ2 T Cells in the Bone Marrow of Myeloma Patients: A Paradigm of Microenvironment-Induced Immune Suppression
2018
Vγ9Vδ2 T cells are non-conventional T cells with a natural inclination to recognize and kill cancer cells. Malignant B cells, including myeloma cells, are privileged targets of Vγ9Vδ2 T cells in vitro. However, this inclination is often lost in vivo due to multiple mechanisms mediated by tumor cells and local microenvironment. Multiple myeloma (MM) is a paradigm disease in which antitumor immunity is selectively impaired at the tumor site. By interrogating the immune reactivity of bone marrow (BM) Vγ9Vδ2 T cells to phosphoantigens, we have revealed a very early and long-lasting impairment of Vγ9Vδ2 T-cell immune functions which is already detectable in monoclonal gammopathy of undetermined …
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…
Prognostic Role of Plasma PD-1, PD-L1, pan-BTN3As and BTN3A1 in Patients Affected by Metastatic Gastrointestinal Stromal Tumors: Can Immune Checkpoin…
2021
Gastrointestinal stromal tumors (GISTs) represent 1% of all primary gastrointestinal tumors. Immune surveillance is often overcome by cancer cells due to the activation of immunoregulatory molecules such as programmed death protein (PD-1) and its ligand PD-L1, and butyrophilin sub-family 3A/CD277 receptors (BTN3A). Because several studies demonstrated that tumor PD-1 and PD-L1 expression may have a prominent prognostic function, this investigation aimed to discover if soluble forms of these molecules may be useful in predicting survival of metastatic GIST (mGIST) patients. Through specific ad hoc developed ELISA assays not yet available on the market, the circulating PD-1, PD-L1, BTN3A1, an…
A “Lymphocyte MicroRNA Signature” as Predictive Biomarker of Immunotherapy Response and Plasma PD-1/PD-L1 Expression Levels in Patients with Metastat…
2020
Introduction of checkpoint inhibitors resulted in durable responses and improvements in overall survival in advanced RCC patients, but the treatment efficacy is widely variable, and a considerable number of patients are resistant to PD-1/PD-L1 inhibition. This variability of clinical response makes necessary the discovery of predictive biomarkers for patient selection. Previous findings showed that the epigenetic modifications, including an extensive microRNA-mediated regulation of tumor suppressor genes, are key features of RCC. Based on this biological background, we hypothesized that a miRNA expression profile directly identified in the peripheral lymphocytes of the patients before and a…
Extracellular Vesicles and Tumor-Immune Escape: Biological Functions and Clinical Perspectives
2020
The modulation of the immune system is one of the hallmarks of cancer. It is now widely described that cancer cells are able to evade the immune response and thus establish immune tolerance. The exploration of the mechanisms underlying this ability of cancer cells has always attracted the scientific community and is the basis for the development of new promising cancer therapies. Recent evidence has highlighted how extracellular vesicles (EVs) represent a mechanism by which cancer cells promote immune escape by inducing phenotypic changes on different immune cell populations. In this review, we will discuss the recent findings on the role of tumor-derived extracellular vesicles (TEVs) in re…
Prognostic role of soluble PD-1 and BTN2A1 in overweight melanoma patients treated with nivolumab or pembrolizumab: finding the missing links in the …
2023
Individual response to immune checkpoint inhibitors (ICIs) is currently unpredictable in patients with melanoma. Recent findings highlight a striking improvement in the clinical outcomes of overweight/obese patients treated with ICIs, which seems driven, at least in part, by programmed cell death protein 1 (PD-1)-mediated T-cell dysfunction. A putative role of butyrophilins (BTNs) is under investigation as a novel mechanism of cancer immune evasion and obesity-associated inflammation. This study investigates the role of baseline plasma levels of soluble PD-1 (sPD-1), soluble programmed cell death ligand 1 (sPD-L1), BTN2A1 (sBTN2A1), BTN3A1 (sBTN3A1), along with body mass index (BMI), as pr…