Evolution of delayed resistance to immunotherapy in a melanoma responder.

ABSTRACT: Despite initial responses^1-3, most melanoma patients develop resistance⁴ to immune checkpoint blockade (ICB). To understand the evolution of resistance, we studied 37 tumor samples over 9 years from a patient with metastatic melanoma with complete clinical response to ICB followed by delayed recurrence and death. Phylogenetic analysis revealed co-evolution of seven lineages with multiple convergent, but independent resistance-associated alterations. All recurrent tumors emerged from a lineage characterized by loss of chromosome 15q, with post-treatment clones acquiring additional genomic driver events. Deconvolution of bulk RNA sequencing and highly multiplexed immunofluorescence (t-CyCIF) revealed differences in immune composition among different lineages. Imaging re

SUBMITTER: Liu D 

PROVIDER: S-EPMC8474080 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature