Myeloid-derived suppressor cells down-regulate L-selectin expression on CD4+ and CD8+ T cells
Erica M Hanson1, Virginia K Clements, Pratima Sinha
1Department of Biological Sciences, University of Maryland Baltimore County, Baltimore, MD 21250, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|June 26, 2009
Summary
Myeloid-derived suppressor cells (MDSC) reduce L-selectin on T cells, hindering their ability to reach tumors. This mechanism impairs the body's antitumor immune response, a critical finding for cancer research.
Area of Science:
- Immunology
- Cancer Biology
- Cellular Trafficking
Background:
- Effective antitumor immunity relies on T cell activation and trafficking to tumors.
- L-selectin (CD62L) is crucial for directing naive lymphocytes to lymph nodes and inflammatory sites like tumors.
- Advanced cancer is associated with immune suppression driven by myeloid-derived suppressor cells (MDSC).
Purpose of the Study:
- To investigate the relationship between T cell L-selectin levels and MDSC in cancer.
- To determine if MDSC directly down-regulate L-selectin on naive T cells.
- To elucidate the mechanism by which MDSC may inhibit antitumor immunity.
Main Methods:
- Correlation analysis of T cell L-selectin and MDSC levels in cancer patients.
- Co-culture experiments of naive T cells with tumor-induced MDSC.
- Analysis of L-selectin levels in T cells from aged mice and mice treated to elevate MDSC.
- Investigation of ADAM17 expression on MDSC.
Main Results:
- Reduced T cell L-selectin inversely correlates with MDSC levels in cancer.
- MDSC directly reduce L-selectin on naive T cells in vitro and in vivo.
- MDSC likely use ADAM17 to cleave L-selectin's ectodomain.
- MDSC-mediated L-selectin down-regulation impairs T cell homing to tumor sites.
Conclusions:
- MDSC directly reduce L-selectin levels on naive T cells.
- This reduction impairs T cell homing and activation, thereby inhibiting antitumor immunity.
- MDSC represent a significant mechanism of immune suppression in cancer.
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