Techniques: Immune cell profiling of melanoma biopsies to predict responses to anti-PD-1 mAbs

Immune cell profiling of melanoma biopsies could help predict patient responses to anti-PD-1 mAbs. In a longitudinal study of 46 patients treated with the anti-PD-1 mAb Keytruda pembrolizumab after failure to respond to anti-cytotoxic T-lymphocyte associated protein 4 (CTLA4; CD152) mAbs, immunohistochemical analysis of tumor biopsies showed high tumor numbers of immune cells expressing CD3, CD4, CD8, PD-1, PD-L1 and/or lymphocyte-activation gene 3 (LAG3; CD223) within the first 1.4 months of Keytruda therapy were more predictive of positive long-term responses than pretreatment baseline measurements of the same cell populations. In an independent study in two cohorts of 20 melanoma patients receiving Keytruda or the anti-PD-1 mAb Opdivo nivolumab, profiling of tumor biopsies with multiparameter flow cytometry showed that patients with at least 20% of tumor-infiltrating CD8+ T cells expressing high levels of PD-1 and CTLA-4 had response rates of 85.7% (12/14) and 78.6% (11/14), whereas patients with less than 20% had response rates of 0% (0/6 in each cohort). Next steps could include validating the results in larger patient cohorts.

Merck & Co. Inc. and Taiho Pharmaceutical Co. Ltd. market Keytruda, a humanized IgG4 mAb against PD-1, to treat melanoma, non-small cell lung cancer (NSCLC) and head and neck cancer, and have the mAb in Phase I through Phase III testing for multiple other cancers...