Impaired antigen presentation and potent phagocytic activity identifying tumor-tolerant human monocytes.
Monocyte exposure to tumor cells induces a transient state in which these cells are refractory to further exposure to cancer. This phenomenon, termed "tumor tolerance", is characterized by a decreased production of proinflammatory cytokines in response to tumors. In the past, we found that this effect comprises IRAK-M up regulation and TLR4 and CD44 activation. Herein we have established a human model of tumor tolerance and have observed a marked down-regulation of MHCII molecules as well as the MHCII master regulator, CIITA, in monocytes/macrophages. These cells combine an impaired capability for antigen presentation with potent phagocytic activity and exhibit an M2-like phenotype. In addition circulating monocytes isolated from Chronic Lymphocytic Leukemia patients exhibited the same profile as tumor tolerant cells after tumor ex vivo exposition.
Laboratory of TumorImmunology, IdiPAZ, La Paz Hospital, Madrid, Spain.
Alessandra
A
Soares-Schanoski
Teresa
T
Jurado
Raúl
R
Córdoba
María
M
Siliceo
Carlos Del
CD
Fresno
Vanesa
V
Gómez-Piña
Victor
V
Toledano
Maria T
MT
Vallejo-Cremades
Sergio
S
Alfonso-Iñiguez
Arkaitz
A
Carballo-Palos
Irene
I
Fernández-Ruiz
Carolina
C
Cubillas-Zapata
Subhra K
SK
Biswas
Francisco
F
Arnalich
Francisco
F
García-Río
Eduardo
E
López-Collazo
D017951:Antigen Presentation; D006367:HeLa Cells; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008954:Models, Biological; D009000:Monocytes / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology*; D009687:Nuclear Proteins / Q000276:immunology; D010587:Phagocytosis; D015534:Trans-Activators / Q000276:immunology
D000949:Histocompatibility Antigens Class II; D008070:Lipopolysaccharides; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators