Post-ICB Lymphocyte Stability Following Immune Checkpoint Blockade Is Coupled to Mitochondrial Haplotype and Clinical Outcome in Advanced Melanoma

Early biomarkers of durable response to immune checkpoint blockade (ICB) are urgently needed. We identify lymphocyte stability (LS) - preservation of peripheral lymphocyte counts after one cycle of ICB - as an on-treatment predictor of overall survival (OS) in metastatic melanoma (MM): patients with unstable lymphocyte counts (LS-U; post-ICB/baseline [≤]0.8) have markedly increased risk of death. Metabolic profiling of patient T cells demonstrates ICB enhancement of mitochondrial bioenergetics, whilst CD8+ T cells from LS-U patients mount an exaggerated transcriptional response to ICB incor

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