Dexmedetomidine induces immunogenic cancer cell death and sensitizes tumors to PD-1 blockade.

Background: Local anesthetics promote anticancer immune responses. A machine learning-based algorithm trained with information on the biological effects and molecular descriptors of analgesics, anesthetics, hypnotics and opioids predicted antitumor effects for dexmedetomidine (DEX). DEX is a sedative acting as an alpha2-adrenoceptor (ADRA2) agonist.

RIPK1 inhibition in malignant cells potentiates immunotherapy and radiotherapy outcome.

Apoptosis, necroptosis and pro-inflammatory NF-κB-dependent signaling are repressed by receptor-interacting serine/threonine-protein kinase 1 (RIPK1). A recent paper in describes a small molecule inducing the proteolytic degradation of RIPK1. In preclinical experiments, this RIPK1 inhibitor improved the anticancer efficacy of radiotherapy, immunotherapy (with PD-1 blockade) and radioimmunotherapy (with CTLA-4 blockade).

Building multiscale models with PhysiBoSS, an agent-based modeling tool.

Multiscale models provide a unique tool for analyzing complex processes that study events occurring at different scales across space and time. In the context of biological systems, such models can simulate mechanisms happening at the intracellular level such as signaling, and at the extracellular level where cells communicate and coordinate with other cells. These models aim to understand the impact of genetic or environmental deregulation observed in complex diseases, describe the interplay between a pathological tissue and the immune system, and suggest strategies to revert the diseased phenotypes.

Targeted opening of the blood-brain barrier facilitates doxorubicin/anti-PD-1-based chemoimmunotherapy of glioblastoma.

Doxorubicin is a prototypical inducer of immunogenic cell death (ICD) that sensitizes to subsequent immunotherapy by PD-1 blockade. However, this systemic drug combination fails against glioblastoma, hidden behind the blood-brain barrier (BBB). A recent work delineates a biophysical method for BBB permeabilization that yields effective preclinical effects of chemoimmunotherapy.

Building multiscale models with PhysiBoSS, an agent-based modeling tool.

Multiscale models provide a unique tool for studying complex processes that study events occurring at different scales across space and time. In the context of biological systems, such models can simulate mechanisms happening at the intracellular level such as signaling, and at the extracellular level where cells communicate and coordinate with other cells. They aim to understand the impact of genetic or environmental deregulation observed in complex diseases, describe the interplay between a pathological tissue and the immune system, and suggest strategies to revert the diseased phenotypes.

Autoimmunity affecting the biliary tract fuels the immunosurveillance of cholangiocarcinoma.

Cholangiocarcinoma (CCA) results from the malignant transformation of cholangiocytes. Primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are chronic diseases in which cholangiocytes are primarily damaged. Although PSC is an inflammatory condition predisposing to CCA, CCA is almost never found in the autoimmune context of PBC.

Dynamical Boolean Modeling of Immunogenic Cell Death.

As opposed to the standard tolerogenic apoptosis, immunogenic cell death (ICD) constitutes a type of cellular demise that elicits an adaptive immune response. ICD has been characterized in malignant cells following cytotoxic interventions, such as chemotherapy or radiotherapy. Briefly, ICD of cancer cells releases some stress/danger signals that attract and activate dendritic cells (DCs).