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Chemokine Receptor ...
Chemokine Receptor Expression on T Cells Is Modulated by CAFs and Chemokines Affect the Spatial Distribution of T Cells in Pancreatic Tumors
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- Gorchs, L (författare)
- Karolinska Institutet
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Oosthoek, M (författare)
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- Yucel-Lindberg, T (författare)
- Karolinska Institutet
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- Moro, CF (författare)
- Karolinska Institutet
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- Kaipe, H (författare)
- Karolinska Institutet
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(creator_code:org_t)
- 2022-08-06
- 2022
- Engelska.
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:15
- Relaterad länk:
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http://kipublication...
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https://doi.org/10.3...
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Abstract
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- The accumulation of T cells is associated with a better prognosis in pancreatic cancer. However, the immunosuppressive tumor microenvironment, largely composed by cancer-associated fibroblasts (CAFs), can prevent T cells from reaching the tumor nests. We examined how human CAFs modulated chemokine receptors known to be associated with T cell trafficking, CXCR3 and CCR5, and T cell exclusion, CXCR4. CAFs decreased the expression of CXCR3 and CCR5 but increased CXCR4 expression in both 2D and 3D cultures, affecting the migratory capacity of T cells towards CXCL10. An immunohistochemistry analysis showed that very few T cells were found in the tumor nests. Within the stroma, CD8+ T cells were localized more distantly from the malignant cells whereas CD4+ T cells were more equally distributed. Tumor tissues with a high production of chemokines were associated with less T cell infiltration when the whole tissue was analyzed. However, when the spatial localization of CD8+ T cells within the tissue was taken into account, levels of CXCR3 ligands and the CCR5 ligand CCL8 showed a positive association with a high relative T cell infiltration in tumor-rich areas. Thus, CXCR3 ligands could mediate T cell trafficking but CAFs could prevent T cells from reaching the malignant cells.
Publikations- och innehållstyp
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- art (ämneskategori)
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Cancers
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