Abstract 4074: A 10 million cell atlas of cytokine-stimulated PBMCs via high-throughput combinatorial single cell RNA sequencing

Abstract Cytokines, secreted by immune cells, are essential for coordinating immune responses against pathogens and abnormal cells, such as those found in cancer. Despite their critical role, a comprehensive understanding of how many different types of immune cells respond to individual cytokines remains elusive. To begin to address this challenge, we created a comprehensive single cell atlas of immune responses to 90 cytokines, profiling the single cell transcriptomes of 10 million PBMCs from 12 donors after 24 hours of treatment. We identified 18 cell types, resulting in the analysis of 19, 440 experimental conditions. Our analysis revealed gene expression changes that are both cell type- and donor-specific, uncovering responses even in rare immune cell populations that are difficult to capture in smaller datasets. Furthermore, we also identified a small number of cytokines that induced changes in cell type proportions after cytokine treatment. Given the limited number of publicly available large-scale single cell studies, we also provide an updated, detailed analysis workflow to encourage researchers to produce similarly scaled-up datasets. By sharing this comprehensive dataset and methodology, we aim to empower the scientific community to scale single cell experiments and drive advancements in immunology, immuno-oncology, cancer biology, and beyond. Citation Format: Joey Pangallo, Efthymia Papalexi, Simone Marrujo, Bryan Hariadi, Crina Curca, Alexa Suyama, Maria Nigos, Oliver Sanderson, Hoai Nguyen, Vuong Tran, Ajay Sapre, Olivia Kaplan, Sarah Schroeder, Alec Salvino, Ryan Koehler, Gokhan Demirkan, Gary Geiss, Charles Roco, Alexander Rosenberg. A 10 million cell atlas of cytokine-stimulated PBMCs via high-throughput combinatorial single cell RNA sequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4074.