Abstract
Viruses can escape destruction by the immune system by exploitation of the chemokine-chemokine receptor system. It is less established whether human cancers can adopt similar strategies to evade immunologic control. In this study, we show that advanced cutaneous T cell lymphoma (CTCL) is associated with selective and efficient inactivation of CXCR3-dependent T cell migration. Our studies demonstrate that this alteration is at least in part due to CXCR3 down-regulation in vivo by elevated serum levels of CXCR3 ligands. The T cell population most affected by this down-regulatory mechanism are CD8+ cytotoxic effector T cells. In CTCL patients, cytotoxic effector T cells have strongly reduced surface CXCR3 expression, accumulate in peripheral blood, but are virtually absent from CTCL tumor lesions, indicating an inability to extravasate into lymphoma tissue. CTCL-associated inactivation of effector cell recruitment may be a paradigmatic example of a new type of immune escape mechanisms shielding the neoplasm from a tumoricidal attack.
| Original language | English |
|---|---|
| Pages (from-to) | 4272-82 |
| Number of pages | 11 |
| Journal | Journal of Immunology |
| Volume | 179 |
| Issue number | 6 |
| Publication status | Published - 15 Sept 2007 |
Keywords
- CD8-Positive T-Lymphocytes
- Cell Membrane
- Cell Movement
- Cells, Cultured
- Down-Regulation
- E-Selectin
- Endosomes
- Endothelial Cells
- G0 Phase
- Humans
- Immunologic Memory
- K562 Cells
- L-Selectin
- Ligands
- Lymphoma, T-Cell, Cutaneous
- Lysosomes
- Receptors, CXCR3
- Receptors, Chemokine
- Skin Neoplasms
- Tumor Cells, Cultured
- Vascular Cell Adhesion Molecule-1