Enhanced antitumor immunity in mice deficient in CD69.
We investigated the in vivo role of CD69 by analyzing the susceptibility of CD69-/- mice to tumors. CD69-/- mice challenged with MHC class I- tumors (RMA-S and RM-1) showed greatly reduced tumor growth and prolonged survival compared with wild-type (WT) mice. The enhanced anti-tumor response was NK cell and T lymphocyte-mediated, and was due, at least in part, to an increase in local lymphocytes. Resistance of CD69-/- mice to MHC class I- tumor growth was also associated with increased production of the chemokine MCP-1, diminished TGF-beta production, and decreased lymphocyte apoptosis. Moreover, the in vivo blockade of TGF-beta in WT mice resulted in enhanced anti-tumor response. In addition, CD69 engagement induced NK and T cell production of TGF-beta, directly linking CD69 signaling to TGF-beta regulation. Furthermore, anti-CD69 antibody treatment in WT mice induced a specific down-regulation in CD69 expression that resulted in augmented anti-tumor response. These data unmask a novel role for CD69 as a negative regulator of anti-tumor responses and show the possibility of a novel approach for the therapy of tumors.
Departmento de Fisiología, Universidad de Barcelona, Barcelona 08080 Spain.
Enric
E
Esplugues
David
D
Sancho
Javier
J
Vega-Ramos
Carlos
C
Martínez
Uta
U
Syrbe
Alf
A
Hamann
Pablo
P
Engel
Francisco
F
Sánchez-Madrid
Pilar
P
Lauzurica
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D006706:Homeostasis; D007694:Killer Cells, Natural / Q000276:immunology; D037181:Lectins, C-Type; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000502:physiology; D015854:Up-Regulation; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D037181:Lectins, C-Type; D016212:Transforming Growth Factor beta; D000099192:CD69 Antigens