Abstract 4699: Pan-cancer single-cell analysis reveals the interactions of SPP1+MMP12+ macrophages with metastasis-initiating cells that drives metastasis

Abstract Advanced understanding of cancer immunology has contributed to a significant decline in cancer deaths in the past few decades. However, there are still vast majority of patients with no effective response for current immunotherapy drugs because of some innate immune cells, particularly macrophages and neutrophils, promoting all steps of malignant progression to metastasis. Therefore, the development of new strategies against these pro-metastatic non-tumor components in the tumor microenvironment is in need. Tumor-associated macrophage (TAMs), as the critical component of tumor microenvironment (TME), display diverse and even opposing function phenotypes, but without systematic investigation on their ubiquitous characteristics across different cancer types. Here, we perform pan-cancer analysis on 92 samples across 6 solid cancer types to profile the TME of normal, primary tumor, metastatic lymph node and distant metastasis at single-cell resolution, illustrating the commonalities/plasticity of heterogenous TAMs. We uncover 21 distinct subtypes of TAMs with varying abundance and biological function in different tissue microenvironment, providing evidence for the plasticity of TAMs. In particular, the enrichment of SPP1+MMP12+ macrophages in the TME of lymph node metastasis, likely interacting with metastasis-initiating cells (MICs), is associated with promoting malignant progression to metastasis and survival stratifications. Multi-color immunofluorescence (mIF) staining for relevant markers is being performed in mouse models and clinical samples for comprehensive validation. Our study comprehensively describes the characteristics and dynamics of TAMs and highlights their heterogeneity and plasticity depending on their surrounding microenvironment. Citation Format: Baifeng Zhang, Dora Lai-wan Kwong, Xin-Yuan Guan. Pan-cancer single-cell analysis reveals the interactions of SPP1+MMP12+ macrophages with metastasis-initiating cells that drives metastasis. [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 4699.