Search results for "Checkpoint Inhibitors"

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…

First-Line Immune Checkpoint Inhibitor-Based Sequential Therapies for Advanced Hepatocellular Carcinoma: Rationale for Future Trials

2021

<b><i>Introduction:</i></b> Atezolizumab (ATEZO) plus bevacizumab (BEVA) represents the new standard of care for the treatment of advanced hepatocellular carcinoma (HCC). However, the choice of the second-line treatment after the failure of immunotherapy-based first-line remains elusive. Taking into account the weaknesses of the available evidence, we developed a simulation model based on available phase III randomized clinical trials (RCTs) to identify optimal risk/benefit sequential strategies. <b><i>Methods:</i></b> A Markov model was built to estimate the overall survival (OS) of sequential first- and second-line systemic treatments. Seque…

Pretreatment metastatic growth rate determines clinical outcome of advanced melanoma patients treated with anti-PD-1 antibodies: a multicenter cohort…

2021

BackgroundCheckpoint inhibitors revolutionized the treatment of metastatic melanoma patients. Although tumor burden and lactate dehydrogenase (LDH) are associated with overall survival (OS), the impact of tumor growth kinetics remains elusive and in part contradictory. The aims of this study were to develop a novel simple and rapid method that estimates pretreatment metastatic growth rate (MGR) and to investigate its prognostic impact in melanoma patients treated with antiprogrammed death receptor-1 (PD-1) antibodies.MethodsMGR was assessed in three independent cohorts of a total of 337 unselected consecutive metastasized stage IIIB–IV melanoma patients (discovery cohort: n=53, confirmation…

INfluenza Vaccine Indication during therapy with Immune checkpoint inhibitors: A multicenter prospective observational study (INVIDIa-2)

2021

BackgroundUntil now, no robust data supported the efficacy, safety and recommendation for influenza vaccination in patients with cancer receiving immune checkpoint inhibitors (ICIs).MethodsThe prospective multicenter observational INfluenza Vaccine Indication During therapy with Immune checkpoint inhibitors (INVIDIa-2) study investigated the clinical effectiveness of influenza vaccination in patients with advanced cancer receiving ICIs, enrolled in 82 Italian centers from October 2019 to January 2020. The primary endpoint was the time-adjusted incidence of influenza-like illness (ILI) until April 30, 2020. Secondary endpoints regarded ILI severity and vaccine safety.ResultsThe study enrolle…

First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (C…

2021

First-line chemotherapy for advanced or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastro-oesophageal junction adenocarcinoma has a median overall survival (OS) of less than 1 year. We aimed to evaluate first-line programmed cell death (PD)-1 inhibitor-based therapies in gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma. We report the first results for nivolumab plus chemotherapy versus chemotherapy alone.In this multicentre, randomised, open-label, phase 3 trial (CheckMate 649), we enrolled adults (≥18 years) with previously untreated, unresectable, non-HER2-positive gastric, gastro-oesophageal junction, or oesophageal adenocarcinoma, …

Immune checkpoint inhibitors plus chemotherapy versus chemotherapy or immune checkpoint inhibitors for first- or second-line treatment of advanced ga…

2019

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To evaluate the efficacy and safety of immune checkpoint inhibitors, alone or in combination with chemotherapy, in people with advanced gastric and gastroesophageal junction adenocarcinoma in first and subsequent treatment lines.

Neurofilament light chain levels reflect outcome in a patient with glutamic acid decarboxylase 65 antibody–positive autoimmune encephalitis under imm…

2020

Neurological immune-mediated side effects are rare but often severe complications of immune checkpoint inhibitor (ICI) treatment. This report describes a severe case of nivolumab/ipilimumab-associated glutamic acid decarboxylase 65-positive autoimmune encephalitis. It proposes neurofilament light chain levels, a biomarker indicating axonal damage, in the cerebrospinal fluid and serum as a putative novel biomarker for this diagnostically and therapeutically challenging entity with an often unfavorable outcome. Additionally, we provide an overview of previous reports of patients developing autoimmune encephalitis under ICI treatment.

Understanding mechanisms of primary resistance to checkpoint inhibitors will lead to precision immunotherapy of advanced gastric cancer

2019

Programmed Death Ligand 1 (PD-L1) as a Predictive Biomarker for Pembrolizumab Therapy in Patients with Advanced Non-Small-Cell Lung Cancer (NSCLC).

2019

Recently, immunotherapy has been shown to be an effective and helpful therapeutic option for the treatment of advanced non-small-cell lung cancer (NSCLC). The activity of antitumor T cells may be restored through the checkpoint blockade using anti-programmed death 1 or anti-programmed death ligand 1 (PD-L1) antibodies, showing, in several cancer patients, an increased progression-free survival and overall survival compared with classical chemotherapy. As recently shown by several studies, the PD-L1 expression levels in tumors may offer a selection criterion for patients to predict their immunotherapy response. In particular, NSCLC patients with high tumor PD-L1 levels (proportional score ≥ …