Abstract 2684: Pan-cancer neutrophil profiling illuminates anti-tumor antigen-presenting potency

Abstract

Abstract Neutrophils, the most abundant and efficient defenders against pathogens, exert opposing functions across cancer types. However, given their short half-life and fragile proliferation, it remains challenging to explore how neutrophils adapt to specific fates in cancer. Here we generated and integrated single-cell neutrophil transcriptomes from 17 cancer types (225 samples, 143 patients). Neutrophils exhibited extraordinary complexity, with 10 distinct cell states along differentiation paths including inflammation, angiogenesis, and antigen presentation. Notably, the antigen-presenting program was associated with favorable survival in most cancers and could be evoked by leucine metabolism and subsequent histone H3K27ac modification. These neutrophils could further invoke both (neo)antigen-specific and antigen-independent T-cell responses. Neutrophil delivery or leucine diet fine-tuned the immune balance to boost anti-PD-1 therapy in various murine cancers. In summary, these data not only unravel the neutrophil divergence across cancers, but also offer therapeutic opportunities such as antigen-presenting neutrophil delivery. Citation Format: Ying Cheng Wu, Jiaqiang Ma, Qiang Gao. Pan-cancer neutrophil profiling illuminates anti-tumor antigen-presenting potency [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2684.