Skip to main content

Immunogenic cell death in anticancer therapy

Objective

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.

Call for proposal

ERC-2012-ADG_20120314
See other projects for this call

Host institution

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Address
Rue De Tolbiac 101
75654 Paris
France
Activity type
Research Organisations
EU contribution
€ 2 500 000
Principal investigator
Guido Peter Krömer (Prof.)
Administrative Contact
Saliha Cantacuzeme (Mrs.)

Beneficiaries (1)

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
France
EU contribution
€ 2 500 000
Address
Rue De Tolbiac 101
75654 Paris
Activity type
Research Organisations
Principal investigator
Guido Peter Krömer (Prof.)
Administrative Contact
Saliha Cantacuzeme (Mrs.)