Supervised clustering of peripheral immune cells associated with clinical response to checkpoint inhibitor therapy in patients with advanced melanoma

Immune therapy with checkpoint inhibitors (CPIs) is a highly successful therapy in many cancers including metastatic melanoma. Still, many patients do not respond well to therapy and there are no blood-borne biomarkers available to assess the clinical outcome. To investigate cellular changes after C...

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Bibliographic Details
Published in:	Immuno-oncology technology Vol. 20; p. 100396
Main Authors:	Kverneland, A.H., Thorsen, S.U., Granhøj, J.S., Hansen, F.S., Konge, M., Ellebæk, E., Donia, M., Svane, I.M.
Format:	Journal Article
Language:	English
Published:	Elsevier Ltd 01-12-2023 Elsevier
Subjects:	biomarkers checkpoint inhibitors immune monitoring immune therapy metastatic melanoma Original supervised clustering immune therapy supervised clustering immune monitoring biomarkers metastatic melanoma checkpoint inhibitors
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Summary:	Immune therapy with checkpoint inhibitors (CPIs) is a highly successful therapy in many cancers including metastatic melanoma. Still, many patients do not respond well to therapy and there are no blood-borne biomarkers available to assess the clinical outcome. To investigate cellular changes after CPI therapy, we carried out flow cytometry-based immune monitoring in a cohort of 90 metastatic melanoma patients before and after CPI therapy using the FlowSOM algorithm. To evaluate associations to the clinical outcome with therapy, we divided the patients based on progression-free survival. We found significant associations with CPI therapy in both peripheral blood mononuclear cell and T-cell subsets, but with the most pronounced effects in the latter. Particularly CD4+ effector memory T-cell subsets were associated with response with a positive correlation between CD27+HLA-DR+CD4+ effector memory T cells in a univariate (odds ratio: 1.07 [95% confidence interval 1.02-1.12]) and multivariate regression model (odds ratio: 1.08 [95% confidence interval 1.03-1.14]). We also found a trend towards stronger accumulation of CD57+CD8+ T cells in non-responding patients. Our results show significant associations between immune monitoring and clinical outcome of therapy that could be evaluated as biomarkers in a clinical setting. [Display omitted] •Checkpoint inhibitor therapy is a very potent cancer therapy but lacks clinical biomarkers for response.•Clustering algorithms can be used with large patient cohorts to phenotype and quantify cellular subsets in flow cytometry.•Checkpoint inhibitor therapy is associated with immunological changes in peripheral blood.•Increase in CD4+ effector memory T cells expressing HLA-DR is significantly associated with long progression-free survival.•Increase in late-differentiated CD8+ T cells is associated to therapy and more pronounced in patients with short progression-free survival.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Authors contributed equally to this work.
ISSN:	2590-0188 2590-0188
DOI:	10.1016/j.iotech.2023.100396