Abstract 4653: Spatial architecture of tumor-infiltrating macrophagesorchestrates tumor immunity and therapeutic response

Abstract

Abstract Tumor-infiltrating macrophages, a major cellular component in the tumor microenvironment (TME), have been proven to be linked with tumor progression and immunotherapy resistance. Tremendous heterogeneity has been revealed for tumor-associated macrophages (TAMs) in different cancer types, however, how these TAM subtypes are localized and interact with tissue ecosystems remains poorly understood. Here, we perform an integrative analysis of TAMs, malignant and non-malignant cells from 10 cancer types, based on single-cell RNA-seq and spatial transcriptomic data. By interrogating the spatial distributions of different TAM subtypes in situ, we reveal spatially restricted developmental, regulation, and functional heterogeneity of TAMs in TME. Different cancer types show distinct TAM subtype enrichments with specific interface architectures, which is potentially shaped by the cellular compositions and spatial niches of tumor cells. Furthermore, the compartmentalized TAM subpopulations can reflect the spatial architecture of surrounding stromal and immune cells, and thus orchestrate tumor immunity and therapeutic response. Our study demonstrates the cellular and molecular underpinnings of TAM heterogeneity and stochastic regulations of TAMs for TME architecture, tumor progression and immunotherapy responses, which will assist in the identification of possible therapeutic targets. Citation Format: Yuanyuan Zhang, Fuduan Peng, Guangsheng Pei, Yunhe Liu, Guangchun Han, Linghua Wang. Spatial architecture of tumor-infiltrating macrophagesorchestrates tumor immunity and therapeutic response. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4653.