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Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma

We conducted a randomized phase II study of neoadjuvant nivolumab versus combined ipilimumab with nivolumab in 23 patients with high-risk resectable melanoma (NCT02519322) and assessed clinical responses and immune correlates. Treatment with combined ipilimumab and nivolumab yielded high response rates (RECIST overall response rate 73%, pathologic complete response rate 45%) but substantial toxicity (73% grade 3 treatment related adverse events), whereas treatment with nivolumab monotherapy yielded modest responses (RECIST overall response rate 25%, pathologic complete response rate 25%) and low toxicity (8% grade 3 treatment related adverse events). Immune correlates of response were identified, demonstrating higher lymphoid infiltrates in responders to both therapies and a more clonal and diverse T cell infiltrate in responders to nivolumab monotherapy. Mutational load was also higher in responders to therapy.

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Dataset ID Description Technology Samples
EGAD00001004352 Illumina HiSeq 2500 30
EGAD00001005803 unspecified 39
EGAD00010001608 MiSeq 59
Publications Citations
Publisher Correction: Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma.
Nat Med 24: 2018 1942
6
neoepiscope improves neoepitope prediction with multivariant phasing.
Bioinformatics 36: 2020 713-720
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B cells and tertiary lymphoid structures promote immunotherapy response.
Nature 577: 2020 549-555
990
Stroma remodeling and reduced cell division define durable response to PD-1 blockade in melanoma.
Nat Commun 11: 2020 853
16
Immune-awakening revealed by peripheral T cell dynamics after one cycle of immunotherapy.
Nat Cancer 1: 2020 210-221
98
Burden of tumor mutations, neoepitopes, and other variants are weak predictors of cancer immunotherapy response and overall survival.
Genome Med 12: 2020 33
49
The T cell receptor repertoire of tumor infiltrating T cells is predictive and prognostic for cancer survival.
Nat Commun 12: 2021 4098
65
Microbiota triggers STING-type I IFN-dependent monocyte reprogramming of the tumor microenvironment.
Cell 184: 2021 5338-5356.e21
150