In:
Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2021-11-16)
Abstract:
Treatment of advanced melanoma with combined immune checkpoint inhibitor (ICI) therapy is complicated in up to 50% of cases by immune-related adverse events (irAE) that commonly include hepatitis, colitis and skin reactions. We previously reported that pre-therapy expansion of cytomegalovirus (CMV)-reactive CD4 + effector memory T cells (T EM ) predicts ICI-related hepatitis in a subset of patients with Stage IV melanoma given αPD-1 and αCTLA-4. Here, we develop and validate a 10-color flow cytometry panel for reliably quantifying CD4 + T EM cells and other biomarkers of irAE risk in peripheral blood samples. Compared to previous methods, our new panel performs equally well in measuring CD4 + T EM cells (agreement = 98%) and is superior in resolving CD4 + CD197 + CD45RA - central memory T cells (T CM ) from CD4 + CD197 + CD45RA + naive T cells (T naive ). It also enables us to precisely quantify CD14 + monocytes (CV = 6.6%). Our new “monocyte and T cell” (MoT) assay predicts immune-related hepatitis with a positive predictive value (PPV) of 83% and negative predictive value (NPV) of 80%. Our essential improvements open the possibility of sharing our predictive methods with other clinical centers. Furthermore, condensing measurements of monocyte and memory T cell subsets into a single assay simplifies our workflows and facilitates computational analyses.
Type of Medium:
Online Resource
ISSN:
1664-3224
DOI:
10.3389/fimmu.2021.765644
DOI:
10.3389/fimmu.2021.765644.s001
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2021
detail.hit.zdb_id:
2606827-8
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