Intratumoral induction of CD103 triggers tumor-specific CTL function and CCR5-dependent T-cell retention.
We have reported previously that the interaction of alpha(E)(CD103)beta(7) 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-beta1 receptor triggers CD103 expression on T-cell surface resulting in strong potentiation of antitumor lytic function. Moreover, interaction of alpha(E)beta(7) 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-beta1 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.
Franciszkiewicz
Katarzyna
K
Institut National de la Santé et de la Recherche Médicale U753, Laboratoire Immunologie des Tumeurs Humaines, Interaction Effecteurs Cytotoxiques-Système Tumoral,"Institut Fédératif de Recherche-54, Villejuif, France.
Le Floc'h
Audrey
A
Jalil
Abdelali
A
Vigant
Frédéric
F
Robert
Thomas
T
Vergnon
Isabelle
I
Mackiewicz
Andrzej
A
Benihoud
Karim
K
Validire
Pierre
P
Chouaib
Salem
S
Combadière
Christophe
C
Mami-Chouaib
Fathia
F
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis* / Q000276:immunology; D015820:Cadherins / Q000276:immunology; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000276:immunology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000276:immunology; D006801:Humans; D039001:Integrin alpha Chains / Q000096:biosynthesis* / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D008175:Lung Neoplasms / Q000097:blood / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D008819:Mice, Nude; D016513:Mice, SCID; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis / Q000276:immunology; D019713:Receptors, CCR5 / Q000096:biosynthesis / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D015703:Antigens, CD; D015820:Cadherins; D039001:Integrin alpha Chains; D016169:Lymphocyte Function-Associated Antigen-1; D011948:Receptors, Antigen, T-Cell; D019713:Receptors, CCR5; C091367:alpha E integrins; D018799:Intercellular Adhesion Molecule-1