We advocate the hypothesis that successful chemotherapeutics can induce a type of tumor cell stress and death that is immunogenic, meaning that the patient’s dying cancer cells serve as a vaccine that stimulates a specific antitum...
ver más
¿Tienes un proyecto y buscas un partner? Gracias a nuestro motor inteligente podemos recomendarte los mejores socios y ponerte en contacto con ellos. Te lo explicamos en este video
Proyectos interesantes
SAF2013-48626-C2-2-R
APOPTOSIS, INMUNIDAD Y CANCER. I. MECANISMOS DE MUERTE CELUL...
91K€
Cerrado
SAF2016-76338-R
ATACANDO AL TUMOR POR VARIOS FLANCOS: QUIMIOTERAPIA INMUNOGE...
254K€
Cerrado
SAF2008-02139
REGULACION DE LA MUERTE CELULAR POR TUMORES Y PATOGENOS COMO...
121K€
Cerrado
RTI2018-094739-B-I00
NUEVOS MECANISMOS DE DESREGULACION DE LA SEÑALIZACION POR CA...
157K€
Cerrado
BES-2016-076722
PAPEL DEL SISTEMA TRAIL/TRAILR EN LA DECISION ENTRE RESPUEST...
93K€
Cerrado
BFU2010-15049
ESTRES OXIDATIVO, APOPTOSIS Y CANCER. IMPLICACIONES DE LA ME...
121K€
Cerrado
Fecha límite de participación
Sin fecha límite de participación.
Descripción del proyecto
We advocate the hypothesis that successful chemotherapeutics can induce a type of tumor cell stress and death that is immunogenic, meaning that the patient’s dying cancer cells serve as a vaccine that stimulates a specific antitumor immune response, which in turn can control (and sometimes even eradicate) residual cancer cells. This is a highly original – and necessarily controversial – breakthrough concept since it challenges previous belief that anticancer chemotherapies act solely on the tumor cells, without any significant involvement of the host immune system. Cell death is usually non-immunogenic, and only a small minority of chemotherapeutic agents can induce immunogenic cell death, which - in contrast to classical apoptosis - is preceded by two types of pre-mortem stress, autophagy (which is required for cellular ATP release, an obligatory signal of immunogenicity) and endoplasmic reticulum (ER) stress (which is required for calreticulin [CRT] exposure at the cell surface, another obligatory signal of immunogenicity). Here, we will explore the hypothesis that cancer cell death is only immunogenic if the two pathways of pre-mortem stress, autophagy and ER stress, are simultaneously activated. Thus, we aim at decoding the anticancer drug-induced cellular pathways that regulate the immunogenicity of cell death. For this, we will trigger cancer cell death preceded by one or the two types of pre-mortem stress in a synthetic system (by genetic manipulation involving inducible transgenes in cancer cells and mice) or by means of selected pharmacological compounds in multiple in vitro and in vivo cancer models, as we monitor the immune-dependent therapeutic response. Moreover, we will investigate the functional links between autophagy, ER stress and immunogenic signaling. Finally, we will explore the translational relevance of these findings on human cancers.