Microbiota-associated immunotherapy resistance caused by deficient PD-L2 - RGMb signaling
Marine Fidelle1,2, Isabelle Lebhar1,2,3, Laurence Zitvogel1,2,3,4
1Gustave Roussy, Villejuif, France.
Oncoimmunology
|July 3, 2023
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.
Insights
Intestinal dysbiosis hinders immunotherapy by upregulating PD-L2/RGMb. Targeting these molecules with antibodies can restore anti-PD-1 treatment effectiveness in patients with gut microbiome imbalances.
Area of Science:
- Immunology
- Microbiome Research
- Cancer Therapy
Background:
- Immunotherapy targeting the PD-L1/PD-1 pathway is a cornerstone of modern cancer treatment.
- Intestinal dysbiosis, an imbalance in gut microbiota, has been linked to variable responses in cancer patients undergoing immunotherapy.
- The precise mechanisms by which dysbiosis affects immunotherapy efficacy remain incompletely understood.
