Predicting anti-PD-1 responders in malignant melanoma from the frequency of S100A9+ monocytes in the blood.

Autor:	Rad Pour S; Department of Medicine, Centre for Molecular Medicine, Karolinska Institutet, Stockholm, Stockholm, Sweden soudabeh.radp@yahoo.com Jesper.tegner@kaust.edu.sa., Pico de Coaña Y; Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden., Demorentin XM; Navarrabiomed, Complejo Hospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), IdiSNA, Pamplona, Spain., Melief J; Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden., Thimma M; Biological and Environmental Sciences and Engineering Division (BESE), KingAbdullah University of Science and Technology KAUST, Thuwal, 23955, Saudi Arabia., Wolodarski M; Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.; Karolinska University Hospital, Stockholm, Sweden., Gomez-Cabrero D; Department of Medicine, Centre for Molecular Medicine, Karolinska Institutet, Stockholm, Stockholm, Sweden.; Navarrabiomed, Complejo Hospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), IdiSNA, Pamplona, Spain.; Biological and Environmental Sciences and Engineering Division (BESE), KingAbdullah University of Science and Technology KAUST, Thuwal, 23955, Saudi Arabia., Hansson J; Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.; Karolinska University Hospital, Stockholm, Sweden., Kiessling R; Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.; Karolinska University Hospital, Stockholm, Sweden., Tegner J; Department of Medicine, Centre for Molecular Medicine, Karolinska Institutet, Stockholm, Stockholm, Sweden soudabeh.radp@yahoo.com Jesper.tegner@kaust.edu.sa.; Biological and Environmental Sciences and Engineering Division (BESE), KingAbdullah University of Science and Technology KAUST, Thuwal, 23955, Saudi Arabia.; Computer, Electrical, and Mathematical Sciences and Engineering Division (CEMSE), KingAbdullah University of Science and Technology KAUST, Thuwal, 23955, Saudi Arabia.
Jazyk:	angličtina
Zdroj:	Journal for immunotherapy of cancer [J Immunother Cancer] 2021 May; Vol. 9 (5).
DOI:	10.1136/jitc-2020-002171
Abstrakt:	Background: While programmed cell death receptor 1 (PD-1) blockade treatment has revolutionized treatment of patients with melanoma, clinical outcomes are highly variable, and only a fraction of patients show durable responses. Therefore, there is a clear need for predictive biomarkers to select patients who will benefit from the treatment. Method: To identify potential predictive markers for response to PD-1 checkpoint blockade immunotherapy, we conducted single-cell RNA sequencing analyses of peripheral blood mononuclear cells (PBMC) (n=8), as well as an in-depth immune monitoring study (n=20) by flow cytometry in patients with advanced melanoma undergoing treatment with nivolumab at Karolinska University Hospital. Blood samples were collected before the start of treatment and at the time of the second dose. Results: Unbiased single-cell RNA sequencing of PBMC in patients with melanoma uncovered that a higher frequency of monocytes and a lower ratio of CD4+ T cells to monocyte were inversely associated with overall survival. Similarly, S100A9 expression in the monocytic subset was correlated inversely with overall survival. These results were confirmed by a flow cytometry-based analysis in an independent patient cohort. Conclusion: Our results suggest that monocytic cell populations can critically determine the outcome of PD-1 blockade, particularly the subset expressing S100A9, which should be further explored as a possible predictive biomarker. Detailed knowledge of the biological role of S100A9+ monocytes is of high translational relevance. Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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