January 2012- Cell autophagy: a key to the success of chemotherapy via a specific immune response


Contrary to what is believed, chemotherapy alone does not destroy a tumor. In addition to its direct effects of cytotoxicity to cancerous cells, it stimulates the patient’s immune response to the tumor. Guido Kroemer, professor and hospital consultant at the Université Paris Descartes - HEGP (AP-HP) and his team working on “Apoptosis, cancer and immunity” (Gustave Roussy Cancer Institute, Inserm, Université Paris-Sud, les Cordeliers Reasearch Unit) have demonstrated that immunogenic cancer cell death causes this process. The destruction of cancer cells by chemotherapy stimulates a specific immune response that acts against residual tumor cells, and this immune response is responsible for the long-term effects of cancer treatment.

We can say that certain chemotherapeutic agents convert the tumor cells into the form of a therapeutic vaccine by inducing immunogenic cancer cell death. Before it becomes immunogenic, cancer cell death must pass through an autophagy stage where the cells are partly destroyed by external stresses, notably those caused by cancer treatments.
The dying tumor cells release warning messages, including ATP (molecules that store energy), that recruit the immune cells and allow a targeted response against the residual cancer cells. Extracellular ARP attracts dentritic cells, that play a critical role in the immune system within the tumor. These cells alert and activate the T lymphocytes, that can specifically attack the residual tumor cells. This discovery opens up a whole new field of research into the link between chemotherapy and the specific anti-tumor immune response. “Our results show that tumor cell autophagy is vital in boosting the patient’s immune system”, explains Mr. Guido Kroemer.

Publication
G. Autophagy-dependent anticancer immune responses induced by chemotherapeutic agents in mice.
Michaud M, Martin I, Sukkuwala A, Adjemian S, Ma Y, Pellegati P, Shen S, Kepp 0, Scoazec M, Mignot G, Rello-Varona S, Tailler M, Menger L, Vacchelli E, Galluzzi L, Ghirïnghelli F, Galluzzi L, di Virgilio F, Zitvogel L, Kroemer G.
Science. 2011 Dec16;334:1573-1577
Guido Kroemer, M.D., Ph.D. PU-PH

Related themes
1 INSERM, U848, Villejuif, France
2 Université Paris Descartes, Sorbonne Paris Cité, Paris, France
3 Metabolomics Platform, Institut Gustave Roussy, Villejuif, France
4 Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France
5 Centre de Recherche des Cordeliers, Paris, France

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