Microbiota-associated immunotherapy resistance caused by deficient PD-L2 - RGMb signaling

Marine Fidelle; Isabelle Lebhar; Laurence Zitvogel; Guido Kroemer

doi:10.1080/2162402X.2023.2224679

Microbiota-associated immunotherapy resistance caused by deficient PD-L2 - RGMb signaling

Oncoimmunology. 2023 Jun 28;12(1):2224679. doi: 10.1080/2162402X.2023.2224679. eCollection 2023.

Authors

Marine Fidelle^{1

2}, Isabelle Lebhar^{1

2

3}, Laurence Zitvogel^{1

2

3

4}, Guido Kroemer^{5

6

7}

Affiliations

¹ Gustave Roussy, Villejuif, France.
² Equipe Labellisée Par la Ligue Contre le Cancer, Villejuif, France.
³ Department of Biology, Center of Clinical Investigations in Biotherapies of Cancer (CICBT) BIOTHERIS, Villejuif, France.
⁴ Faculty of Medicine, Université Paris Saclay, Le Kremlin-Bicêtre, France.
⁵ Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Center, Université Paris Saclay, Villejuif, France.
⁶ Centre de Recherche des Cordeliers, Equipe Labellisée Par la Ligue Contre le Cancer, Institut Universitaire de France, Université de Paris, Sorbonne Université, Villejuif, France.
⁷ Department of Biology, Institut du Cancer Paris Carpem, Hôpital Européen Georges Pompidou, AP-HP, Villejuif, France.

Abstract

In a recent paper in Nature, Park et al. propose a mechanism through which intestinal dysbiosis compromises the efficacy of immunotherapy targeting the PD-L1/PD-1 interaction. Dysbiosis may upregulate a pair of checkpoint molecules, i.e. PD-L2 interacting with RGMb. Antibodies targeting PD-L2/RGMb can restore responses to PD-1 blockade in the context of dysbiosis.

Publication types

Editorial
Research Support, Non-U.S. Gov't

MeSH terms

Drug Resistance
Dysbiosis*
Gastrointestinal Microbiome
Humans
Immunotherapy / adverse effects
Programmed Cell Death 1 Receptor*
Signal Transduction

Substances

Programmed Cell Death 1 Receptor

Grants and funding

The work was supported by the Agence Nationale de la Recherche Association pour la Recherche sur le Cancer Cancéropôle Ile de France European Research Area Network on Cardiovascular Diseases [ERA-CVD, MINOTAUR]; Fondation Leducq Fondation pour la Recherche Médicale Institut National Du Cancer Institut National de la Santé et de la Recherche Médicale Institut Universitaire de France Ligue Contre le Cancer [EL2016.LNCC (VT/PLP)]; the RHU Torino Lumière the LabEx Immuno-Oncology [ANR-18-IDEX-0001]; Fondation Carrefour the European Union Horizon 2020 Project Oncobiome Gustave Roussy Odyssea a donation by Elior Chancellerie des universités de Paris (Legs Poix) Association “Le Cancer du Sein, Parlons-en!” AMMICa US23/CNRS UMS3655 the SIRIC Cancer Research and Personalized Medicine (CARPEM) the RHU Torino Lumière; the Seerave Foundation the European Union’s Horizon Europe research and innovation program [PREVALUNG-EU 101095604]; the SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE) Seerave Foundation