INVESTIGADORES
ZWIRNER Norberto Walter
congresos y reuniones científicas
Título:
Recruitment of dendritic cells to tumor microenvironment mediated by NK cell derived chemotactic factors
Autor/es:
RAFFO IRAOLAGOITÍA, XIMENA LUCÍA; SPALLANZANI, RAÚL GERMÁN; ZIBLAT, ANDREA; DOMAICA, CAROLINA INÉS; ZWIRNER, NORBERTO WALTER; FUERTES, MERCEDES BEATRIZ
Lugar:
Los Cocos
Reunión:
Congreso; 61a Reunión Anual de la Sociedad Argentina de Inmunología; 2013
Institución organizadora:
Sociedad Argentina de Inmunología
Resumen:
Contrary to
preconceptions, spontaneous T cell priming occurs frequently in response to a
growing tumor. It has recently been reported that antitumor CD8+ T cell priming is dependent on
dendritic cells (DC), however the innate immune mechanisms that promote their
recruitment to tumors remain ill-defined. We have previously reported that
Natural Killer (NK) cells constitute a critical component for the antitumor
immune response since antigen-specific CD8+ T cell priming was severely reduced in
NK cell-depleted mice compared to non-depleted mice. Although NK cells can
produce chemokines upon cytokine stimulation, a role of NK cells in DC
recruitment has not been pursued. Therefore, the aim of this work was
to study if NK cells can induce the migration of DC to tumors, in vitro and in vivo. To address this, C57BL/6 mice were subcutaneously
challenged with MC57 fibrosarcoma cells and the tumor infiltrating immune cells
were studied at early stages by flow cytometry. We observed an early DC (CD3-B220-CD11c+)
and NK cell (DX5+CD3-) infiltration followed by CD8+ T cells. NK cell-depleted mice showed a significant decrease in DC tumor infiltration compared to control mice six days
after tumor challenge (p<0.05). Moreover, we observed a positive correlation
between the number of NK cells and activated DCs (CD3-B220-CD11c+CD86+) infiltrating the tumors (p<0.001;
r=0.87). In order to determine if tumor-activated NK cells are able to attract
DCs in vitro,
supernatants from isolated NK
cells co-cultured with MC57 cells
were tested for their chemotactic activity towards bone marrow-derived DCs
(BMDCs) in a transwell cell migration assay. While
robust chemoattractive activity for BMDCs was detected in the supernatants of
co-cultures, no similar activity was detectable in the supernatants of resting
NK cells or MC57 cells cultured alone (p<0.05). Our results suggest that NK
cells can recruit DCs to the tumor
microenvironment, enhancing the spontaneous antitumor
T cell priming.