In this study, we used single-cell RNA and T cell receptor (TCR) sequencing (scRNA+TCRαβ-Seq), flow cytometry, TCRβ-Seq, and serum protein profiling together with ex vivo functional validations to analyze immune cell responses to anti–LAG-3+anti–PD-1 treatment (relatlimab+nivolumab, phase I, ClinicalTrials.gov NCT01968109) in pretreatment blood samples and blood samples taken 1 and 3 months after therapy from 40 patients with metastatic melanoma (Figure 1). Here, PDCD1 is linked to metastatic melanoma.