Spatial Location of SPP1⁺TAMs and Mutually Exclusive Subsets Based on Single-Cell and Transcriptome Data

Area of Science:

• Oncology
• Immunology
• Genomics

Background:

• Lung adenocarcinoma (LUAD) progression involves complex cellular interactions.
• Tumor-associated macrophages (TAMs) are key players in the tumor microenvironment.
• Understanding TAM subsets is crucial for targeted LUAD therapies.

Purpose of the Study:

• To delineate the distinct subsets and spatial locations of SPP1+ TAMs in LUAD.
• To analyze the polarization, cellular subsets, and spatial distribution of SPP1+ TAMs.
• To provide a basis for precision treatment strategies in LUAD.

Main Methods:

• Analysis of transcriptome data from TCGA, GTEx, and GEO databases.
• Single-cell and spatial transcriptome analysis.
• Immunohistochemical analysis using HPA and local LUAD samples.

Main Results:

• SPP1 is identified as a central regulatory gene in LUAD.
• SPP1+ M2 macrophages are associated with invasive lung carcinoma (ILC), while MARCO+ M2 macrophages are linked to adenocarcinoma in situ (AIS).
• SPP1+ M2 macrophages are located at the tumor edge, potentially increasing invasiveness, and are spatially distinct from MARCO+ M2 macrophages.

Conclusions:

• SPP1+ M2 and MARCO+ M2 macrophages form mutually exclusive subsets in LUAD.
• These distinct macrophage subsets synergistically promote different stages of LUAD progression.
• Targeting these specific TAM subsets may offer novel therapeutic avenues for LUAD.