RESUMO
For successful immunotherapy for cancer, it is important to understand the immunological status of tumor antigen-specific CD8+ T cells in the tumor microenvironment during tumor progression. In this study, we monitored the behavior of B16OVA-Luc cells in mice immunized with a model tumor antigen ovalbumin (OVA). Using bioluminescence imaging, we identified the time series of OVA-specific CD8+ T-cell responses during tumor progression: initial progression, immune control, and the escape phase. As a result of analyzing the status of tumor antigen-specific CD8+ cells in those 3 different phases, we found that the expression of NKG2D defines tumor-reacting effector CD8+ T cells. NKG2D may control the fate and TOX expression of tumor-reacting CD8+ T cells, considering that NKG2D blockade in OVA-vaccinated mice delayed the growth of the B16OVA-Luc2 tumor and increased the presence of tumor-infiltrating OVA-specific CD8+ T cells.
Assuntos
Linfócitos T CD8-Positivos/imunologia , Melanoma Experimental/imunologia , Melanoma Experimental/metabolismo , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/metabolismo , Microambiente Tumoral/imunologia , Animais , Antígenos de Neoplasias/administração & dosagem , Antígenos de Neoplasias/metabolismo , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/farmacocinética , Bromodesoxiuridina/administração & dosagem , Bromodesoxiuridina/farmacocinética , Interferon gama/deficiência , Interferon gama/genética , Luciferases/metabolismo , Medições Luminescentes/métodos , Linfócitos do Interstício Tumoral/imunologia , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ovalbumina/administração & dosagem , Ovalbumina/metabolismo , Neoplasias Cutâneas/patologia , Vacinação/métodosRESUMO
IMPLICATIONS: Considering the importance of GSTA4 in controlling IFNγ responsiveness and the metastatic potential of other melanoma cells, our results highlight a novel mechanism whereby cancer cells escape from host immunity and gain metastatic ability by acquiring resistance to oxidative stress responses through the upregulation of GSTA4.