Intratumoral Induction of CD103 Triggers Tumor-Specific CTL Function and CCR5-Dependent T-Cell Retention
| Autor: | Christophe Combadière, Thomas Robert, Abdelali Jalil, Audrey Le Floc’h, Katarzyna Franciszkiewicz, Pierre Validire, Andrzej Mackiewicz, Isabelle Vergnon, Karim Benihoud, Salem Chouaib, Fathia Mami-Chouaib, Frédéric Vigant |
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| Rok vydání: | 2009 |
| Předmět: |
Cancer Research
Lung Neoplasms Receptors CCR5 Chemokine receptor CCR5 T cell Antigen presentation Receptors Antigen T-Cell Mice Nude chemical and pharmacologic phenomena Mice SCID Mice Lymphocytes Tumor-Infiltrating Antigens CD Cell Movement Mice Inbred NOD Carcinoma Non-Small-Cell Lung Cell Line Tumor medicine Animals Humans Cytotoxic T cell Lymphocytes Tumor microenvironment biology hemic and immune systems Cadherins Intercellular Adhesion Molecule-1 Lymphocyte Function-Associated Antigen-1 CTL medicine.anatomical_structure Oncology Peripheral blood lymphocyte Immunology biology.protein Cancer research Integrin alpha Chains CD8 T-Lymphocytes Cytotoxic |
| Zdroj: | Cancer Research. 69:6249-6255 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-08-3571 |
| Popis: | We have reported previously that the interaction of αE(CD103)β7 integrin, expressed on a CD8+ tumor-infiltrating lymphocyte (TIL) clone but not on a peripheral blood lymphocyte (PBL) counterpart, with the epithelial marker E-cadherin on human lung tumor cells plays a crucial role in T-cell receptor–mediated cytotoxicity. We show here that both TIL and PBL clones are able to migrate toward autologous tumor cells and that chemokine receptor CCR5 is involved in this process. Adoptive transfer of the PBL clone in the cognate tumor engrafted in nonobese diabetic/severe combined immunodeficient mice and subsequent coengagement of T-cell receptor and transforming growth factor-β1 receptor triggers CD103 expression on T-cell surface resulting in strong potentiation of antitumor lytic function. Moreover, interaction of αEβ7 integrin with E-cadherin, but not lymphocyte function-associated antigen-1 with intercellular adhesion molecule-1, promotes CCR5 recruitment at the immunologic synapse formed between TIL and tumor cells, leading to inhibition of T-cell sensitivity to CCL5 chemotactic gradient. These results provide evidence for a role of tumor microenvironment, namely MHC class I–restricted antigen presentation and transforming growth factor-β1 secretion, in regulating the effector phase of tumor-specific CTL response. They also suggest a unique role of CD103 in T-cell retention at the tumor site by a CCR5-dependent mechanism. [Cancer Res 2009;69(15):6249–55] |
| Databáze: | OpenAIRE |
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