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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 introduced mipDVP, an advanced approach integrating highly multiplexed imaging, single-cell laser microdissection, and sensitive mass spectrometry to spatially profile the proteomes of distinct cell populations in a human colorectal and tonsil cancer with high sensitivity. In a colorectal tumor—a representative cold tumor—we uncovered spatial compartmentalization of an immunosuppressive macrophage barrier that potentially impedes T cell infiltration. Spatial proteomic analysis revealed distinct functional states of T cells in different tumor compartments. In a tonsil cancer sample—a hot tumor—we identified significant proteomic heterogeneity among cells influenced by proximity to cytotoxic T cell subtypes. T cells in the tumor parenchyma exhibited metabolic adaptations to hypoxic regions. Our spatially resolved, highly multiplexed strategy deciphers the complex cellular interplay within the tumor microenvironment, offering valuable insights for identifying immunotherapy targets and predictive signatures.

INSTRUMENT(S): Orbitrap Astral, timsTOF SCP

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Tonsil, Colon

DISEASE(S): Tonsil Cancer,Colon Cancer

SUBMITTER: Mario Oroshi

LAB HEAD: Matthias Mann

PROVIDER: PXD057118 | Pride | 2024-12-19

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	Astral.zip	Other
	Astral_pg_matrix.txt	Txt
	ColorectalCancer.zip	Other
	ColorectalCancer_Macrophages.zip	Other
	ColorectalCancer_pg_matrix_Macrophages.txt	Txt

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

Project description: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.

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