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Séminaire

Lundi 27 Septembre 2021
14h
https://teams.microsoft.com/l/meetup-join/19%3ameeting_YzQxZDhkOGYtM2NkZC00NWU1LWJiMzctOTJjODQ4M2E3YzA2%40thread.v2/0?context=%7b%22Tid%22%3a%22183ad437-6002-48ad-8886-c5885ce9be1a%22%2c%22Oid%22%3a%22a8544e4e-fdf2-4f3e-9c14-1678560c1a02%22%7d - Webinar

Decoding and Recoding the Opposing Roles of Interferon and Pattern Recognition Receptor Signaling to Improve Cancer Immunotherapy

Andy Minn

Interferon (IFN) and pattern recognition receptor (PRR) signaling are important for immune activation and the effectiveness of cancer immunotherapies. However, these pathways can also have inhibitory roles due to entwined negative feedback mechanisms that can be exploited by tumors often after chronic stimulation. I will discuss our findings on how these opposing roles are regulated in cancer, how they can contribute to immunotherapy resistance, and approaches we are pursuing to mitigate the inhibitory effects of IFN/PRR signaling.

Orateur(s)

Pr Andy Minn
MD, PhD, Professor

Perelman School of Medicine, University of Pennsylvania (USA)

Invité(e)(s) par

Clotilde Théry
Immunité et cancer (U932)

Institut Curie

Emanuela Romano
Immunité et cancer (U932)

Institut Curie

Hélène Salmon
Immunité et cancer (U932)

Institut Curie

Contact

Elodie Mieville

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My laboratory is focused on understanding the regulation and function of anti-viral signaling pathways, such as interferon and pattern recognition receptors, in cancer progression, immunotherapy response, and immunomodulation. We utilize multi- and high-dimensional data-driven approaches towards both experimental and translational research goals. We have discovered that activation of anti-viral signaling is widespread across multiple cancer types and often involve nucleic acid sensing, endogenous RNAs, exosomes, and interferon networks. Thus, endogenous molecules that participate in “virus mimicry” are pervasive in human cancer. We are investigating how anti-viral and pattern recognition receptors are activated in cancer, both cell intrinsically and through the tumor microenvironment, and their functional significance (Boelens et al., Cell 2014; Nabet et al., Cell, 2017). Due to their immunostimulatory effects, anti-viral and pattern recognition receptor pathways can also be therapeutically exploited. One way is through activation by ablative tumor irradiation, which may underlie the ability of the DNA damage response to stimulate the immune system (Twyman-Saint Victor et al., Nature 2015). However, opposing these immune stimulatory effects are feedback inhibition properties of interferon signaling. Recent efforts have deduced how persistent interferon signaling can “paradoxically” promote resistance to immune checkpoint blockade by inhibiting both adaptive and innate immune cells (Benci et al., Cell 2016, Benci and Johnson et al., Cell 2019). Working with colleagues, many of our studies using mouse models have been performed together with analogous clinical trials (ClinicalTrials.gov IDs: NCT02303990, NCT02639026, NCT03646617, and NCT03425006) in order to corroborate pre-clinical results with evidence from human patients. In this way, laboratory findings can inform the design of next generation clinical trials.