Blass & Keskin (2025): Melanoma NeoVax analysis: IFNg single-cell RNAseq

Introduction

This is a book that contains all code to reproduce figures related to scRNAseq analysis of IFNg data associated with Blass & Keskin, et al (2025)

Note that while the code is identical, this book was rendered after final manuscript figures were generated and thus minor differences may arise, particularly for steps that are non-deterministic or rely on random number generators.

Enhanced adjuvanticity of a personal neoantigen vaccine generates potent immunity in melanoma

Eryn Blass, Derin B. Keskin, Chloe R. Tu, Cleo Forman, Allison Vanasse, Haley E. Sax, Bohoon Shim, Vipheaviny Chea, Nawoo Kim, Isabel Carulli, Jackson Southard, Haoxiang Lyu, Wesley Lu, Micah Rickles-Young, Alexander B. Afeyan, Oriol Olive, Ambica Mehndiratta, Haley Greenslade, Keerthi Shetty, Joanna Baginska, Ilana Gomez-Diaz, Allison Nau, Kathleen L. Pfaff, Andrew Gans, Elizabeth I Buchbinder, Tamara A. Sussman, Megan L Insco, Charles H. Yoon, Scott J. Rodig, Sachet A. Shukla, Shuqiang Li, Jon C. Aster, David A. Braun, Carrie Cibulskis, Nir Hacohen, Donna S. Neuberg, A Giobbie-Hurder, Kenneth J. Livak, Edward F. Fritsch, Giacomo Oliveira, Jeremy M. Simon, Catherine J. Wu, Patrick A. Ott

Abstract

Personalized neoantigen-targeting vaccines have great promise, but current delivery strategies are suboptimal. Since antigen availability and effective T cell priming are critical for maximal immunogenicity, we tested a synthetic long peptide vaccine formulated with Montanide, poly-ICLC, and locally administered ipilimumab in addition to systemic nivolumab in 10 patients with melanoma. These personalized vaccines generated de novo ex vivo T cell responses against the majority of immunizing neoepitopes in all 9 fully vaccinated patients, and ex vivo CD8+ T cell responses in 6 of 9. Vaccination induced hundreds of circulating and intratumoral T cell receptor (TCR) clonotypes that were distinct from those arising after PD-1 inhibition. By linking the vaccine neoantigen specificity of T cell clonotypes with single cell phenotypes in tumors, we demonstrate remodeling of the intratumoral T cell repertoire following vaccination. These observations show that multi-pronged immune adjuvanticity can boost T cell responses to neoantigen-targeting vaccines