CD40 Pathway and IL-2 Expression Mediate the Differential Outcome of Colorectal Cancer Patients with Different <i>CSF1R</i> c.1085 Genotypes
Colony-stimulating factor 1 receptor (CSF-1R) acts as the receptor for colony stimulating factor 1, a cytokine that controls the production, differentiation, and function of macrophages. Prior studies showed cancer patients harboring germline <i>CSF1R</i> c.1085A>G genetic variant had...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-11-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/22/12565 |
| Summary: | Colony-stimulating factor 1 receptor (CSF-1R) acts as the receptor for colony stimulating factor 1, a cytokine that controls the production, differentiation, and function of macrophages. Prior studies showed cancer patients harboring germline <i>CSF1R</i> c.1085A>G genetic variant had better survival. Here, primary tumor samples from a stage III colorectal cancer (CRC) cohort were analyzed by a targeted gene expression assay containing 395 immune-related genes to study the immune mechanism underlying the different outcomes. CRC patients with <i>CSF1R</i> c.1085 genotype A_G had a better disease-free and overall survival than those with <i>CSF1R</i> genotype A_A. Compared to the group of patients without <i>CSF1R</i> variant, higher <i>CD40LG</i> expression, a surface marker of T cells, was found in the tumor tissues of patients with <i>CSF1R</i> c.1085 variant. In parallel with the higher <i>CD40LG</i> gene expression, immunofluorescent staining also showed more CD3<sup>+</sup>CD40L<sup>+</sup> T cell infiltrates in tumors with <i>CSF1R</i> c.1085 genotype A_G. Moreover, higher IL-2 expression, known to be regulated by CD40 pathway, was also observed in tumors with <i>CSF1R</i> c.1085 genotype A_G than genotype A_A. Higher IL-2 expression generated by the interaction of CD40 ligand and CD40 between T cells and macrophages with <i>CSF1R</i> c.1085A>G variant is the potential mechanism explaining the different outcomes. |
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| ISSN: | 1661-6596 1422-0067 |