Immunosuppressive role of SPP1-CD44 in the tumor microenvironment of intrahepatic cholangiocarcinoma assessed by single-cell RNA sequencing
Purpose To demonstrate the biological function of Secreted Phosphoprotein 1( SPP1 ) and its immune suppressive role in the progression intrahepatic cholangiocarcinoma (ICC). Methods We collected 62,770 cells’ published transcriptome data of nine patients whose paired adjacent liver and tumor tissues...
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Published in | Journal of cancer research and clinical oncology Vol. 149; no. 9; pp. 5497 - 5512 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Berlin/Heidelberg
Springer Berlin Heidelberg
01.08.2023
Springer Nature B.V |
Subjects | |
Online Access | Get full text |
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Summary: | Purpose
To demonstrate the biological function of Secreted Phosphoprotein 1(
SPP1
) and its immune suppressive role in the progression intrahepatic cholangiocarcinoma (ICC).
Methods
We collected 62,770 cells’ published transcriptome data of nine patients whose paired adjacent liver and tumor tissues were both available. We applied differential gene expression analysis to screen potential ICC marker genes, survival analysis to verify the prognostic value of
SPP1
, and correlation analysis to decipher factors that are related to
SPP1
expression. The CellChat was used to distinguish interactions between cancer and T cells. CytoSig was applied to query cytokines that modulate
CD44
. Further, we established a proliferation score and correlated the score with inhibitory signals to determine the proliferation-suppressive function of SPP1-CD44.
Results
SPP1
expression is significantly upregulated in tumoral epitheliums, and patients with higher
SPP1
expression have worse survival (
P
< 0.05). Tumor cells communicate with T cells via SPP1-CD44 interactions. The average expression of
SPP1
in malignant cells (SPP1m) and
CD44
in T cells (CD44t) is moderately negatively correlated with T cell proliferation score. Immunosuppressive cytokine TGFβ-3 identified as an inducer of
CD44
and was significantly negatively correlated with proliferation score (
R
= − 0.88,
P
< 0.01), and the negative correlation was aggravated in samples with high
CD44
expression.
Conclusion
SPP1
is a prognostic marker of ICC and is associated with the genome heterogeneity. SPP1-CD44 hinders sustained proliferation of T cells, but immunosuppressive T cells in the tumor microenvironment may evade this inhibition by reducing
CD44
expression. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0171-5216 1432-1335 |
DOI: | 10.1007/s00432-022-04498-w |