Abstract 45P
Background
Monocyte subpopulations and myeloid-derived suppressor cells (MDSCs) are altered in certain diseases, including cancer. Circulating HLA-DR+ blood monocytes can be discriminated into classical (CM, CD14++CD16-), intermediate (IM, CD14++CD16+), and non-classical monocytes (NCM, CD14+CD16++). MDSCs, a monocyte-related cell type, are specified as CD14+CD16-HLA-DR-CD11b+CD33+ and are further distinguished into early (E-MDSCs, CD14-CD15-), polymorphonuclear (PMN-MDSC, CD14-CD15+) and monocytic MDSCs (M-MDSCs, CD14+CD15-). We aimed to investigate the distribution of monocyte subsets and MDSCs in cancer patients receiving immune checkpoint inhibition-based (ICI) therapy to analyse their feasibility as a biomarker for predicting clinical response to ICI-based therapy.
Methods
Monocyte subsets and MDSCs were characterised in whole blood using a novel 14-colour flow cytometry approach based on specific cell surface markers. The panel discriminates both cell types reliably from lymphocytes, granulocytes, natural killer cells, and platelets. For methodological setup, a control cohort with healthy volunteers (n=10) was included to subsequently analyse blood from patients (n=10 each) with non-small cell lung cancer, head and neck squamous cell carcinoma, and pancreatic cancer before ICI treatment initiation and at the first time point of re-staging.
Results
Monocyte subset distribution in healthy individuals was shown to be constant over a period of six weeks (CM 83.34±6.64% vs. 82.02±5.65%, IM 2.73±1.49% vs. 3.33±1.07%, NCM 13.91±5.35% vs. 14.64±5.02%; baseline vs. follow-up), whereas MDSCs displayed greater differences (total MDSCs 0.33±0.32% vs. 0.37±0.17%, E-MDSCs 16.18±15.23% vs. 4.90±3.22%, PMN-MDSCs 7.75±4.91% vs. 10.02±7.78%, M-MDSCs 60.39±16.09% vs. 77.89±9.38%; baseline vs. follow-up).
Conclusions
These preliminary results confirmed that monocyte subpopulations and MDSCs could be identified simultaneously using the newly established flow cytometry panel, and thus, the basis for future analysis of both cell types in whole blood from cancer patients undergoing ICI-based therapy was provided.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Univ. Prof. Dr. Matthias Preusser.
Funding
Christian Doppler Research Association and Roche.
Disclosure
M. Preusser: Financial Interests, Personal, Advisory Board: Bayer, Bristol Myers Squibb, Novartis, Gerson Lehrman, CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, BMJ Journals, MedMedia, AstraZeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, Sanofi, Merck Sharp & Dohme, Tocagen, Adastra, Gan & Lee Pharmaceuticals; Financial Interests, Institutional, Research Grant, Clinical Trials and research: Boehringer Ingelheim, Bristol Myers Squibb, Roche, Daiichi Sankyo, Merck Sharp & Dohme, Novocure, GlaxoSmithKline, AbbVie; Non-Financial Interests, Leadership Role, Brain Tumor Group Chair: EORTC; Non-Financial Interests, Leadership Role, EANO President: EANO. A.S.S. Berghoff: Financial Interests, Personal, Invited Speaker: Roche, Bristol Myers Squibb, Merck, AstraZeneca; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Daiichi Sankyo, Roche. All other authors have declared no conflicts of interest.