Search results for "checkpoint"

Trial Watch: Adoptively transferred cells for anticancer immunotherapy

2017

IF 7.719; International audience; Immunotherapies aimed at strengthening immune effector responses against malignant cells are growing at exponential rates. Alongside, the impressive benefits obtained by patients with advanced melanoma who received adoptively transferred tumor-infiltrating lymphocytes (TILs) have encouraged the scientific community to pursue adoptive cell transfer (ACT)-based immunotherapy. ACT involves autologous or allogenic effector lymphocytes that are generally obtained from the peripheral blood or resected tumors, expanded and activated ex vivo, and administered to lymphodepleted patients. ACT may be optionally associated with chemo- and/or immunotherapeutics, with th…

Responsiveness to anti-PD-1 and anti-CTLA-4 immune checkpoint blockade in SB28 and GL261 mouse glioma models.

2018

Immune checkpoint blockade (ICB) is currently evaluated in patients with glioblastoma (GBM), based on encouraging clinical data in other cancers, and results from studies with the methylcholanthrene-induced GL261 mouse glioma. In this paper, we describe a novel model faithfully recapitulating some key human GBM characteristics, including low mutational load, a factor reported as a prognostic indicator of ICB response. Consistent with this observation, SB28 is completely resistant to ICB, contrasting with treatment sensitivity of the more highly mutated GL261. Moreover, SB28 shows features of a poorly immunogenic tumor, with low MHC-I expression and modest CD8(+) T-cell infiltration, suggest…

POTENTIAL APPLICATIONS OF LIQUID BIOPSY IN IMMUNOTHERAPY: ROLE OF EXOSOMES, MICRORNAS AND PLASMA EXPRESSION LEVELS OF IMMUNE CHECKPOINTS IN PATIENTS …

2023

Cell Cycle: The Life Cycle of a Cell

2013

“Where a cell arises, there must be a previous cell”. This early statement of Rudolf Virchow already points to the process that is called cell cycle. It describes a series of events leading to cell division and duplication and can be sectioned into phases that are controlled by a collection of proteins interacting with each other, the cyclines and the cycline-dependent kinases. It is mandatory that DNA replication is conservative meaning that its structure and sequence remain unaltered while the DNA is duplicated before the cell actually divides. Checkpoints are responsible for the supervision, proteins such as p53 and RB being the key protagonists in cell cycle control. Upon DNA damage rec…

Immune Checkpoint Inhibitors and Cardiotoxicity: An Analysis of Spontaneous Reports in Eudravigilance

2021

Introduction Immune checkpoint inhibitors (ICIs) are widely used in the treatment of many cancers as they improve clinical outcomes. However, ICIs have also been associated with the development of immune-related adverse drug reactions (ADRs). Among immune-related ADRs, cardiac immune-related ADRs are rare, but also associated with high mortality rates. Objective The objective of this study was to evaluate the occurrence of cardiac ADRs reported with ICIs in the European spontaneous reporting system. Methods We retrieved individual case safety reports on ICI-induced cardiac ADRs from the website of suspected ADR (www.adrreports.eu) of the European pharmacovigilance database (Eudravigilance).…

Aryl hydrocarbon receptor-dependent cell cycle arrest in isolated mouse oval cells

2013

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor, which mediates toxic responses to environmental pollutants, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds. Besides its well known role in induction of xenobiotic metabolizing enzymes, for instance CYP1A1, the AhR is also involved in tumor promotion in rodents although the underlying mechanisms are still poorly understood. Additionally, the AhR is known to regulate cellular proliferation, which might result in either inhibition or stimulation of proliferation depending on the cell-type studied. Potential targets in hepatocarcinogenesis are liver oval (stem/progenitor) cells. In the pres…

Enhancing the Activation and Releasing the Brakes: A Double Hit Strategy to Improve NK Cell Cytotoxicity Against Multiple Myeloma

2018

Natural killer (NK) cells are innate lymphocytes with a strong antitumor ability. In tumor patients, such as multiple myeloma (MM) patients, an elevated number of NK cells after stem cell transplantation (SCT) has been reported to be correlated with a higher overall survival rate. With the aim of improving NK cell use for adoptive cell therapy, we also addressed the cytotoxicity of patient-derived, cytokine-stimulated NK cells against MM cells at specific time points: at diagnosis and before and after autologous stem cell transplantation. Remarkably, after cytokine stimulation, the patients' NK cells did not significantly differ from those of healthy donors. In a small cohort of MM patients…

Abemaciclib: safety and effectiveness of a unique cyclin-dependent kinase inhibitor

2020

Introduction: The discovery and the clinical availability of novel cyclin-dependent kinases 4 and 6 inhibitors have profoundly changed the therapeutic scenario of metastatic hormone receptor-positive breast carcinoma. Among these inhibitors, abemaciclib can induce potent and sustained cell cycle arrest and immune system stimulation. Areas covered: This review summarizes the safety profile and clinical efficacy data on abemaciclib alone or in combination with aromatase inhibitors or fulvestrant in metastatic hormone receptor-positive breast carcinoma. The management of patients treated with abemaciclib is the object of this paper. Expert opinion: As shown in phase 2 and 3 clinical trials on …

Regulación del factor transcripcional Whi7 y la proteinquinasa C en el proceso de Start y el checkpoint de integridad del DNA

2019

Start es el principal punto de control del ciclo celular en el que las células se comprometen a una nueva ronda de división celular. Este punto de control implica la activación irreversible de un programa transcripcional por los complejos Cdc28-Cln a través de la inactivación del represor transcripcional de Start Whi5. En este trabajo se proporcionan nuevas claves sobre cómo Whi7, una proteína relacionada a nivel de secuencia con Whi5, reprime Start. Nuestros resultados demuestran que Whi7 es un parálogo genuino de Whi5. Ambas proteínas colaboran en la represión de Start, aunque presentan diferencias importantes en su regulación que convierten a Whi7 en el represor de Start por excelencia e…

CVB3 VP1 interacts with MAT1 to inhibit cell proliferation by interfering with Cdk-activating kinase complex activity in CVB3-induced acute pancreati…

2021

Coxsackievirus B3 (CVB3) belongs to the genus Enterovirus of the family Picornaviridae and can cause acute acinar pancreatitis in adults. However, the molecular mechanisms of pathogenesis underlying CVB3-induced acute pancreatitis have remained unclear. In this study, we discovered that CVB3 capsid protein VP1 inhibited pancreatic cell proliferation and exerted strong cytopathic effects on HPAC cells. Through yeast two-hybrid, co-immunoprecipitation, and confocal microscopy, we show that Menage a trois 1 (MAT1), a subunit of the Cdk-Activating Kinase (CAK) complex involved in cell proliferation and transcription, is a novel interaction protein with CVB3 VP1. Moreover, CVB3 VP1 inhibited MAT…