Early Modification of the Immunometabolism in Patients with Meta-static Melanoma treated by Anti-PD-1 Immunotherapy

Author(s): Marie Lamiaux, Guillaume Paul Grolez, Paola Corazao, Olivier Morales, Marie Boileau, Olivier Ernst, Philippe Marchetti, Jérôme Kluza, Laurent Mortier, Nadira Delhem

Background: Currently, 60 to 70% of patients treated with anti-PD1 for metastatic mel-anoma have innate or acquired resistance under immunotherapy. However, new data demon-strate a link between metabolic changes and the acquisition of immune cell functions and could be used as a potential biomarker of the antitumour response.

Methods: This is a prospective and translational pilot study conducted in the Dermatology Department of Lille University Hospital. All included patients with advanced melanoma were treated with anti-PD-1 immunotherapy. Blood samples were taken before and 3 weeks after the first cycle of anti-PD-1. Tumour response was assessed after 3 and 6 months of immunotherapy.

Results: Patients were enrolled from March 2018 to March 2019. After 3 weeks of anti-PD-1, we found an early increase in reserve respiratory capacity in patients who responded to immunotherapy, while non-responders or pa-tients with stable disease showed no changes. Interestingly, we also identified early changes in the OCR/ECAR ratio from one cycle of anti-PD-1 using patient PBMCs, which correlated linearly and significantly with tumour response at 6 months (p = 0.045).

Conclusions: Evaluation of the OCR/ECAR ratio from patient PBMCs could be used as a potential marker of early response to anti-PD-1 immunotherapy. It would help evaluate new protocols such as combinations or se-quential treatments in melanoma, or even be applied in other types of cancers treated with an-ti-PD-1.