Identification of an Immature Subset of PMN-MDSC Correlated to Response to Checkpoint Inhibitor Therapy in Patients with Metastatic Melanoma

Françoise Gondois-Rey (1, 2) , Magali Paul (1, 2) , Florence Alcaraz (1, 2) , Sarah Bourass (1, 2) , Jilliana Monnier (3) , Nausicaa Malissen (3) , Jean-Jacques Grob (1, 2, 3) , Annika Bruger (4, 5) , Pierre van Der Bruggen (4, 5) , Caroline Gaudy-Marqueste (1, 2, 3) , Daniel Olive (1, 2)

1 CRCM - Centre de Recherche en Cancérologie de Marseille
2 IPC - Institut Paoli-Calmettes
3 TIMONE - Hôpital de la Timone [CHU - APHM]
4 UCL - Université Catholique de Louvain = Catholic University of Louvain
5 WELBIO - Walloon Excellence in Life sciences and BIOtechnology [Liège]

PMN-MDSCs support tumor progression and resistance to ICI therapy through their suppressive functions but their heterogeneity limits their use as biomarkers in cancer. Our aim was to investigate the phenotypic and functional subsets of PMN-MDSCs to identify biomarkers of response to ICI therapy. We isolated low-density CD15+ PMNs from patients with metastatic melanoma and assessed their immune-suppressive capacities. Expression of CD10 and CD16 was used to identify mature and immature subsets and correlate them to inhibition of T cell proliferation or direct cytotoxicity. Frequencies of the PMN-MDSCs subsets were next correlated to the radiological response of 36 patients receiving ICI therapy. Mature activated cells constituted the major population of PMN-MDSCs. They were found in a higher proportion in the pre-treatment blood of patients non responders to ICI. A subset of immature cells characterized by intermediate levels of CD10 and CD16, the absence of expression of SIRPα and a strong direct cytotoxicity to T cells was increased in patients responding to ICI. The paradoxical expansion of such cells during ICI therapy suggests a role of PMNs in the inflammatory events associated to efficient ICI therapy and the usefulness of their monitoring in patients care.

Mots clés: PMN-MDSC; immune suppression; immune-checkpoint therapy; metastatic melanoma; signal regulatory protein alpha

Domaines: Cancer

Françoise Gondois-Rey, Magali Paul, Florence Alcaraz, Sarah Bourass, Jilliana Monnier, et al.. Identification of an Immature Subset of PMN-MDSC Correlated to Response to Checkpoint Inhibitor Therapy in Patients with Metastatic Melanoma. Cancers, 2021, 13 (6), pp.1362. ⟨10.3390/cancers13061362⟩. ⟨hal-03623050⟩