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Omics · study · 2026

The immune cell atlas reveals mechanisms of immune evasion and LAG3 as a novel target in mouse models of breast cancer metastasis

Listed in NCBI GEO

including triple negative breast cancer (TNBC).

Description

However, only a minority of patients respond, and there are no biomarkers for patient stratification and prediction of response. Temporal and spatial characterization of the host immune response was interrogated using single cell RNAseq of immune cells from mouse models of TNBC, which covers 5 tissues and 4 time points ranging from tumor-free to late metastatic disease.

Profound changes were observed in immune composition of the bone marrow, lymph nodes, lung and blood at the earliest time point with small tumors and no metastatic disease. In addition, functional markers were altered during tumor progression suggesting broad subversion of immune function in every cell type examined, particularly in the tumor tissue itself. However, evidence of a beneficial immune response was found in lymph nodes but was clearly inactivated in tumor and lung tissues.

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Notably, single cell data was obtained for granulocytes, which is in contrast to most single cell tumor datasets where granulocytes are absent. Importantly, further analysis showed significant elevation of GAL3, the LAG3 ligand, in tumor infiltrating neutrophils and macrophages. Targeting both LAG3 and PD1 showed the highest reduction in tumor size as well as metastatic burden compared with targeting LAG3 alone or PD1 alone.

Together, our results suggest that LAG3 axis is a critical immune evasion mechanism and lymph node cells is likely a valuable source of anti-tumor immunity that could be harnessed for treatment of triple negative breast cancer.

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From keywords
Life Sciences
Inferred from text
Cancer 75% · Disease 75% · RNA sequencing 65%
Provenance · 1 source records, 10 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE31810913 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[disease].local:disease:cancerenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[disease].local:disease:diseaseenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[modality].local:modality:rna-seqenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (65%)
concepts[organism].NCBITaxon:10090source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title