Assuntos
Artrite Reumatoide/complicações , Síndromes de Malabsorção/etiologia , Enteropatias Perdedoras de Proteínas/etiologia , Artrite Reumatoide/tratamento farmacológico , Doenças Autoimunes/tratamento farmacológico , Etanercepte , Feminino , Humanos , Imunoglobulina G/uso terapêutico , Imunossupressores/uso terapêutico , Pessoa de Meia-Idade , Receptores do Fator de Necrose Tumoral/uso terapêuticoRESUMO
Although diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, it is both clinically and morphologically heterogenous. The present study investigates the significance of survivin and a novel monoclonal antibody (MAb), T332, immunohistochemically for predicting the prognoses of DLBCL and its subtypes classified as germinal center B-cell-like type (GCB) and non-GCB type (NGCB) based on the expression profiles of CD10, bcl-6, and MUM1. A total of 60 cases of DLBCL (GCB, n = 22; NGCB, n = 38) were examined for the expression of survivin and T332 antigen. Survivin(+) DLBCL had a significantly worse prognosis (P = 0.01) than survivin(-) cases, as already reported, while survivin(+) GCB or NGCB tended to have poor prognoses (P = 0.06 and 0.07, respectively). However, T332(+) DLBCL and NGCB had significantly more unfavorable prognoses than T332(-) cases (P = 0.01 and 0.02, respectively) while there was no significant survival difference between the T332(+) and T332(-) groups of GCB (P = 0.11). Interestingly DLBCL coexpressing survivin and T332 (n = 13) had a significantly worse prognosis (P = 0.009) than the remaining single positive and double negative cases (n = 31). In conclusion, survivin and the novel MAb, T332, might be a good predictor of DLBCL and its subtypes.
Assuntos
Anticorpos Monoclonais/imunologia , Antígenos de Neoplasias/biossíntese , Linfoma de Células B/patologia , Linfoma Difuso de Grandes Células B/patologia , Proteínas Associadas aos Microtúbulos/biossíntese , Adulto , Idoso , Animais , Antígenos de Neoplasias/imunologia , Feminino , Humanos , Imuno-Histoquímica , Proteínas Inibidoras de Apoptose , Linfoma de Células B/metabolismo , Linfoma Difuso de Grandes Células B/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Proteínas de Neoplasias , Prognóstico , Análise de Sobrevida , SurvivinaRESUMO
The natural killer (NK) cell is one of the key cells in discriminating major histocompatibility complex (MHC) negative 'missing-self' target tumor cells, and interleukin 2 (IL-2) treatment was effective in inducing NK cell activation. In this study, we tried to clarify how poorly-immunogenic murine B16 melanoma could be discriminated in vivo by creating an IL-2 cDNA-transduced immunogene therapy model (B16/IL-2). In vitro study showed that IL-2 introduction did not induce MHC class I. However, immune cells depleted total tumor digest, which consisted of 90% anti-melanoma MM2-9B6-positive cells that revealed B16/IL-2 strongly, and control tumor cells (B16/mock) partially expressed MHC class I in vivo. In the B16/IL-2 model, NK cell infiltration was 10 times higher than B16/mock (7.6 versus 0.73, p=0.017). In addition, the cell surface of CD69-expressing NK cell population was increased in B16/IL-2, and the interferon gamma (IFNgamma) message level in NK cells was significantly increased in B16/IL-2 (p=0.0359). Interestingly, NK cell depletion in vivo completely abolished MHC class I expression on B16/mock, and decreased MHC class I expression and T-cell infiltration in B16/IL-2. These data suggest that NK cells are not only important for missing-self recognition, but are also crucial for induction of tumor cell MHC molecule expression and play an important role in helping acquired immunity to recognize tumor cells.