Secondary resistance to immunotherapy associated with β-catenin pathway activation or PTEN loss in metastatic melanoma.

Background: While cancer immunotherapies including checkpoint blockade antibodies, adoptive T cell therapy, and even some vaccines have given rise to major clinical responses with durability in many cases, a subset of patients who initially respond subsequently develop secondary resistance to therapy. Tumor-intrinsic mechanisms of acquired immunotherapy resistance are incompletely understood.

Methods: Baseline and treatment-resistant tumors underwent molecular analysis via transcriptional profiling or genomic sequencing for oncogenic alterations and histologic analysis for T cell infiltration to investigate mechanisms contributing to T cell exclusion and acquired resistance to immunotherapy.

Single dose denileukin diftitox does not enhance vaccine-induced T cell responses or effectively deplete Tregs in advanced melanoma: immune monitoring and clinical results of a randomized phase II trial.

Background: Depletion of CD25(+) Tregs improves anti-tumor immunity in preclinical models. Denileukin diftitox is a recombinant fusion protein of human IL-2 and diptheria toxin fragment that also can kill CD25(+) T cells. Prior clinical trials of denileukin diftitox suggested reduction of FoxP3(+) Tregs and some clinical responses.

Phase II multicenter study of neoadjuvant biochemotherapy for patients with stage III malignant melanoma.

Purpose: To determine the relapse-free survival, overall survival, and response rate of patients with stage III melanoma treated with neoadjuvant biochemotherapy in a multicenter setting.

Patients And Methods: Patients with pathologically proven stage III melanoma, either via clinical detection or sentinel lymph node positivity, were eligible for enrollment. Patients received two cycles of preoperative biochemotherapy followed by complete regional lymphadenectomy and two postoperative courses of biochemotherapy.