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Development of a Flow Cytometry Assay to Predict Immune Checkpoint Blockade-Related Complications.

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.

SUBMITTER: Schilling HL

PROVIDER: S-EPMC8637156 | biostudies-literature |

REPOSITORIES: biostudies-literature

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