Early decrease of blood myeloid-derived suppressor cells during checkpoint inhibition is a favorable biomarker in metastatic melanoma.

BACKGROUND

The need for reliable clinical biomarkers to predict which patients with melanoma will benefit from immune checkpoint blockade (ICB) remains unmet. Several different parameters have been considered in the past, including routine differential blood counts, T cell subset distribution patterns and quantification of peripheral myeloid-derived suppressor cells (MDSC), but none has yet achieved sufficient accuracy for clinical utility.

METHODS

Here, we investigated potential cellular biomarkers from clinical routine blood counts as well as several myeloid and T cell subsets, using flow cytometry, in two independent cohorts of a total of 141 patients with stage IV M1c melanoma before and during ICB.

RESULTS

Elevated baseline frequencies of monocytic MDSCs (M-MDSC) in the blood were confirmed to predict shorter overall survival (OS) (HR 2.086, p=0.030) and progression-free survival (HR 2.425, p=0.001) in the whole patient cohort. However, we identified a subgroup of patients with highly elevated baseline M-MDSC frequencies that fell below a defined cut-off during therapy and found that these patients had a longer OS that was similar to that of patients with low baseline M-MDSC frequencies. Importantly, patients with high M-MDSC frequencies exhibited a skewed baseline distribution of certain other immune cells but these did not influence patient survival, illustrating the paramount utility of MDSC assessment.

CONCLUSION

We confirmed that in general, highly elevated frequencies of peripheral M-MDSC are associated with poorer outcomes of ICB in metastatic melanoma. However, one reason for an imperfect correlation between high baseline MDSCs and outcome for individual patients may be the subgroup of patients identified here, with rapidly decreasing M-MDSCs on therapy, in whom the negative effect of high M-MDSC frequencies was lost. These findings might contribute to developing more reliable predictors of late-stage melanoma response to ICB at the individual patient level. A multifactorial model seeking such markers yielded only MDSC behavior and serum lactate dehydrogenase as predictors of treatment outcome.

Informations de copyright

© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: TA reports institutional grants from SkylineDx, institutional grants and personal fees from Novartis, institutional grants from NeraCare, personal fees from BMS, institutional grants from Sanofi, personal fees from CeCaVa, personal fees from Pierre Fabre, outside the submitted work. NW reports an advisory role for Pierre Fabre and Sanofi, consultant's honoraria from Novartis, and has received travel support from AbbVie and Amgen outside the submitted work. FM reports receiving commercial research grants from Novartis and Roche; and has received travel support and/or speaker’s fees and/or advisor’s honoraria by Novartis, Roche, Bristol-Myers Squibb, Merck Sharp & Dohme and Pierre Fabre. PT has received travel support and/or speaker’s fees and/or advisor’s honoraria by Almirall, Biofrontera, Bristol-Myers Squibb, Curevac, Kyowa Kirin, Merck, Merck Sharp & Dohme, Novartis, Pierre Fabre, Roche, Sanofi and 4SC. CG reports receiving commercial research grants from Bristol-Myers Squibb, Novartis and Roche; and is a consultant/advisory board member for Amgen, Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis and Roche. GP has received speaker’s honoraria from Novartis, Roche, Pfizer, GlaxoSmithKline and Astellas. TE has received travel support and/or speaker’s fees and/or advisor’s honoraria by Sanofi, Novartis, Bristol-Myers Squibb, Merck Sharp & Dohme, Almiral Hermal and Pierre Fabre. BW reports receiving commercial research grants from, is a consultant/advisory board member for and reports receiving travel reimbursement from Bristol-Myers Squibb and Merck Sharp & Dohme. KW-H received commercial research grants from CatalYm GmbH and travel support from Society for Immunotherapy of Cancer. No potential conflicts of interest were disclosed by the other authors.