Mutations Associated with Acquired Resistance to PD-1 Blockade in Melanoma.

ABSTRACT:

Background

Approximately 75% of objective responses to anti-programmed death 1 (PD-1) therapy in patients with melanoma are durable, lasting for years, but delayed relapses have been noted long after initial objective tumor regression despite continuous therapy. Mechanisms of immune escape in this context are unknown.

Methods

We analyzed biopsy samples from paired baseline and relapsing lesions in four patients with metastatic melanoma who had had an initial objective tumor regression in response to anti-PD-1 therapy (pembrolizumab) followed by disease progression months to years later.

Results

Whole-exome sequencing detected clonal selection and outgrowth of the acquired resistant tumors and, in two of the four patients, revealed resistance-associated loss-of-functio

SUBMITTER: Zaretsky JM 

PROVIDER: S-EPMC5007206 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature