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1000
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Abstract/Summary
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Indolent (lepidic) and aggressive (micropapillary, solid, and poorly differentiated acinar) histologic subtypes often
coexist within a tumor tissue of lung adenocarcinoma (LUAD), but the molecular features associated with different
subtypes and their transitions remain elusive. Here, we combine spatial transcriptomics and multiplex
immunohistochemistry to elucidate molecular characteristics and cellular plasticity of distinct histologic subtypes of
LUAD. We delineate transcriptional reprogramming and dynamic cell signaling that determine subtype progression,
especially hypoxia-induced regulatory network. Different histologic subtypes exhibit heterogeneity in dedifferentiation
states. Additionally, our results show that macrophages are the most abundant cell type in LUAD, and identify different
tumor-associated macrophage subpopulations that are unique to each histologic subtype, which might contribute to
an immunosuppressive microenvironment. Our results provide a systematic landscape of molecular profiles that drive
LUAD subtype progression, and demonstrate potentially novel therapeutic strategies and targets for invasive lung
adenocarcinoma.
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