Cell autophagy: a key to the success of chemotherapy via a specific

Press Release
20/12/2011
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.
cellule tumorale
stress induit par la chimiothérapie
Autophagie
dégradation du cytoplasme et d’organites
dans des vésicules fusionnées avec des
lysosomes
Apoptose
Evolution extrême de l’autophagie vers la
mort de la cellule avec libération d’ATP
libération d’ATP
recrutement des cellules immunitaire
cellule activé dendritique
Activation des lymphocytes T
Puis destruction des cellules tumorales
encore présentes
lymphocyte T
cellule tumorale résiduelle
Tumor cell
Chemotherapy-illicited stress
Autophagy
Destruction of cytoplasm and organites in
vesicles that have fused with lysosomes
Apoptosis
The programmed terminal evolution of
autophagy towards death of a cell and
release of ATP
Release of ATP
Recruiting immune cells
Activated dendtritic cell
Activation of T lymphocytes
Followed by destruction of residual tumor
cells
T lymphocyte
Residual tumor cell
The process of immunogenic autophagy
We have to understand that the autophagy process is often inhibited in tumor cells, which
causes the dying cells to release ATP and so reduces the therapeutic efficiency in the
immune system. Scientists have discovered a way of increasing the therapeutic response in
these cases. They inhibited the enzyme that breaks down extracellular ATP, thus increasing
the concentration of these energy-storing molecules within the tumor. They also noted that
by re-establishing higher concentrations of extracellular ARP, this increased recruiting of
immune cells and enhanced the effects of chemotherapy. So this could prove to be an
additional possibility of treatment for patients with types of cancer where there is little or no
autophagy. These efficient treatments are still at the highly experimental stage. Assessment
has still to be carried out in mice, followed by clinic tests on human subjects.
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, RelloVarona 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
Contact presse
Université Paris Descartes
Alice Tschudy & Pierre-Yves Clausse
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