Cancer cells regulate lymphocyte recruitment and leukocyte-endothelium interactions in the tumor-draining lymph node
| Autor: | Christine M'rini, Carine Jiguet-Jiglaire, Renaud Colisson, Talal Al Saati, Gérard Bouche, Jean-Philippe Girard, Virginie Carriere, Elisabeth Bellard, François Amalric |
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| Rok vydání: | 2005 |
| Předmět: |
Cancer Research
Chemokine Skin Neoplasms Lymphocyte High endothelial venules Melanoma Experimental Mice medicine Cell Adhesion Leukocytes Tumor Cells Cultured Animals Lymphocytes L-Selectin Lymph node Antigen Presentation Membrane Glycoproteins biology Chemokine CCL21 Melanoma Acquired immune system medicine.disease Mice Inbred C57BL P-Selectin medicine.anatomical_structure Oncology Chemokines CC Lymphatic Metastasis Immunology biology.protein Female Lymph Nodes Endothelium Lymphatic Peripheral lymph CCL21 |
| Zdroj: | Cancer research. 65(24) |
| ISSN: | 0008-5472 |
| Popis: | The physiologic function of the secondary lymphoid organs to recruit large numbers of naïve lymphocytes increases the probability that antigens encounter their rare, sometimes unique, specific T lymphocytes and initiate a specific immune response. In peripheral lymph nodes (LNs), this recruitment is a multistep process, initiated predominantly within the high endothelial venules (HEVs), beginning with rolling and chemokine-dependent firm adhesion of the lymphocytes on the venular endothelium surface. We report here that, in C57BL/6 mice, the recruitment of naïve lymphocytes is impaired in LNs draining a B16 melanoma tumor. Intravital microscopy analysis of the tumor-draining LNs revealed that this effect is associated with an important defect in lymphocyte adhesion in the HEVs and a progressive decrease in the expression of the LN chemokine CCL21. In parallel with these effects, the tumor up-regulated, essentially through a P-selectin–dependent mechanism, the rolling and sticking of circulating polymorphonuclear cells within the LN low-order venules where few rolling and sticking events are usually observed. These effects of the tumor were independent of the presence of metastasis into the LN and occurred as long as the tumor developed. Together, these results indicate that the tumor proximity disturbs the LN physiology by modifying the molecular, spatial, and cellular rules that usually control leukocyte-endothelium interactions into the peripheral LNs. In addition, they emphasize a new role for the low-order venules of the peripheral LNs, which compared with the HEVs, seem to be the preferential port of entry for cells linked to inflammatory processes. (Cancer Res 2005; 65(24): 11639-48) |
| Databáze: | OpenAIRE |
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