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Deciphering functional tumor-immune crosstalk through highly multiplexed imaging and deep visual proteomics

ABSTRACT: Deciphering the intricate tumor-immune interactions within the microenvironment is crucial for advancing cancer immunotherapy. Here, we developed a novel approach integrating highly multiplexed imaging, laser microdissection, and deep visual proteomics to spatially profile the proteomes of 21 distinct cell populations in human colorectal and tonsil cancers with high sensitivity. In colorectal tumors, we uncovered an immunosuppressive macrophage barrier impeding T cell infiltration and regionally altering lymphocyte proteomes. Spatial proteomic analysis revealed distinct functional states of T cells in different tumor compartments. In tonsil cancer, we identified significant tumor cell proteomic heterogeneity influenced by proximity to specific T cell subtypes. Tumor-infiltrating T cells exhibited metabolic adaptations and enhanced stress resilience, enabling migration into hypoxic regions. Our spatially-resolved, highly multiplexed strategy provides a powerful tool to decipher the complex cellular interplay within the tumor microenvironment, with implications for identifying new immunotherapy targets and signatures.

INSTRUMENT(S): Orbitrap Astral, timsTOF SCP

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): B Cell, Tonsil, T Cell, Epithelial Cell, Plasma Cell, Colon, Macrophage

DISEASE(S): Tonsil Cancer,Colon Cancer

SUBMITTER: Mario Oroshi

LAB HEAD: Matthias Mann

PROVIDER: PXD051891 | Pride | 2024-09-16

REPOSITORIES: Pride

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			Action	DRS
	ColorectalCancer.zip	Other
	ColorectalCancer_pg_matrix.tsv	Tabular
	Metadata.xlsx	Xlsx
	TonsilCancer.zip	Other
	TonsilCancer_3Plex_Library.zip	Other

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