PhD student – INSERM U1160, Intestinal Immunity in Inflammation and Cancer - Hôpital Saint Louis, Paris
« The 3IC team works on the intestinal immunity in inflammation and cancer, and more specifically on T cells. The intestine presents a particular immune system, constantly stimulated by exogenous antigens from food, commensal microbiota or pathogens. Specific regulations balance the immune response between tolerance of microbiota and food antigens, and protection against pathogens. This immune homeostasis is crucial and its perturbation are involved in several pathologies. Upon epithelial stress and continuous inflammation, an abnormal proinflammatory immune response can induce autoimmune reactions and chronic inflammation diseases, whereas an excessive tolerant phenotype established an immunosuppressive microenvironment favourable to cancer progression. In this tumor context, an antitumor T cell response is clearly engaged but the upregulation of immunosuppressive markers, like the immune checkpoints, allow the tumor immune escape. Immunotherapies targeting these markers, anti-PD-1 and anti-CTLA-4, were developed but presented a weak efficacy in colorectal cancer (CRC). New therapeutic strategies are necessary. In this project, we studied the antitumor T cell response involved in human CRC. Based on a prospective cohort, our objectives were to better characterize this response to find new potential target for immunotherapy and test their efficacy in our innovative autologous coculture model. We focused on several different pathways including CD39 and CD73. »
Contact IRCM : Laurent GROS
Nanolive, Genève, Suisse
Contact IRCM : Alexandre Djiane
Nanolive, Genève, Suisse
Contact IRCM : Alexandre Djiane
Institute of Cancer Research, Medical University of Vienna, Austria
"Clinical evidence shows that, following initial response to treatment, drug-resistant cancer cells frequently evolve, and eventually most tumors become resistant to all available therapies. The most straightforward cause of therapy resistance is linked to cellular alterations that prevent drugs to act on their target. Upregulation of cell membrane efflux transporters of the ATP-binding cassette (ABC) superfamily leads to simultaneous resistance against structurally and functionally unrelated chemotherapeutic agents. In particular, P-glycoprotein (Pgp, MDR1), the product of ABCB1 gene, was shown to be expressed in several drug resistant malignancies. Based on the correlation of P-glycoprotein expression and function with unfavorable treatment response, it is universally accepted that pharmacological modulation of the MDR phenotype has the potential to significantly increase the efficacy of currently available anticancer therapies. Unfortunately, despite a few early successes, clinical trials conducted with Pgp inhibitors did not fulfill this expectation, failing to confirm clinical benefit. Failure of the trials led to a setback in research, and the shutdown of the pharmaceutical development of transporter inhibitors for the improvement of anticancer therapy. Yet the “transporter problem” has not vanished, as evidenced by new studies supporting the relevance and benefit of research on the role of ABC transporters in clinical drug resistance. Failure of the inhibitors has boosted research in other directions, exploring the possibility to evade efflux, or to exploit the paradoxical sensitivity associated with efflux-based drug resistance mechanisms. In this talk I will describe new approaches to combating multidrug-resistant cancer, including the development of drugs that engage, evade or exploit efflux by P-glycoprotein."
Contact IRCM : Charles Theillet
Le séminaire sera diffusé par Zoom. Un lien sera envoyé par mail quelques jours avant la date
This will be a Zoom webinar. A link will be sent by email in due time.
Institute of Cancer Research, Medical University of Vienna, Austria
"Clinical evidence shows that, following initial response to treatment, drug-resistant cancer cells frequently evolve, and eventually most tumors become resistant to all available therapies. The most straightforward cause of therapy resistance is linked to cellular alterations that prevent drugs to act on their target. Upregulation of cell membrane efflux transporters of the ATP-binding cassette (ABC) superfamily leads to simultaneous resistance against structurally and functionally unrelated chemotherapeutic agents. In particular, P-glycoprotein (Pgp, MDR1), the product of ABCB1 gene, was shown to be expressed in several drug resistant malignancies. Based on the correlation of P-glycoprotein expression and function with unfavorable treatment response, it is universally accepted that pharmacological modulation of the MDR phenotype has the potential to significantly increase the efficacy of currently available anticancer therapies. Unfortunately, despite a few early successes, clinical trials conducted with Pgp inhibitors did not fulfill this expectation, failing to confirm clinical benefit. Failure of the trials led to a setback in research, and the shutdown of the pharmaceutical development of transporter inhibitors for the improvement of anticancer therapy. Yet the “transporter problem” has not vanished, as evidenced by new studies supporting the relevance and benefit of research on the role of ABC transporters in clinical drug resistance. Failure of the inhibitors has boosted research in other directions, exploring the possibility to evade efflux, or to exploit the paradoxical sensitivity associated with efflux-based drug resistance mechanisms. In this talk I will describe new approaches to combating multidrug-resistant cancer, including the development of drugs that engage, evade or exploit efflux by P-glycoprotein."
Contact IRCM : Charles Theillet
Le séminaire sera diffusé par Zoom. Un lien sera envoyé par mail quelques jours avant la date
This will be a Zoom webinar. A link will be sent by email in due time.
Institute of Cancer Research, Medical University Vienna
Contact IRCM: Charles Theillet
“Le séminaire sera diffusé en Webinaire Zoom. Le lien sera diffusé 2 jours avant la date prévue. Il sera transmis en salle de séminaire avec une audience limitée pour respecter la distanciation“
Institute of Cancer Research, Medical University Vienna
Contact IRCM: Charles Theillet
“Le séminaire sera diffusé en Webinaire Zoom. Le lien sera diffusé 2 jours avant la date prévue. Il sera transmis en salle de séminaire avec une audience limitée pour respecter la distanciation“
Centre International de Recherche en Infectiologie (CIRI), INSERM /CNRS/ENS, Lyon
Le séminaire aura lieu dans la salle de séminaire avec une audience limitée pour respecter la distanciation et sera aussi diffusé en Webinaire Zoom. Le lien sera diffusé 2 jours avant la date prévue.
Contact IRCM : Claude Sardet