RESUMO
Since the last two decades, rapid progress has been made in the field of cancer immunotherapy relevant to manipulation of adaptative cytotoxic T lymphocytes (CTLs) and innate immunity natural killer (NK) cells as well as antibodies. Many possibilities are now offered for therapeutic purposes contributing to better approaches in treatment of cancer.
Assuntos
Imunoterapia , Neoplasias/terapia , Antígenos de Neoplasias/imunologia , Humanos , Imunidade Inata , Células Matadoras Naturais/imunologia , Neoplasias/imunologia , Linfócitos T Citotóxicos/imunologiaRESUMO
Modulation of cell surface molecules involved in immune recognition and cellular interactions (class I major histocompatibility complex or MHC-I, B7.1 or CD80, integrin alpha4 or CD49d, tetraspanins CD9, CD81) was examined in modified B16 melanoma cells displaying either inhibited IGF-I expression or transfected OVA encoding gene. It was shown that inhibiting IGF-I expression or inserting OVA encoding gene did not lead to modification relevant to the presence of MHC-I or B7.1. However downregulation of tetraspanin CD9 was observed in modified IGF-I but not in OVA encoding gene inserted melanoma cells. Expression of tetraspanin CD81 and integrin alpha4/CD49d remained unchanged. Inoculated into syngeneic recipients, the modified melanoma cells exhibited significant delayed outgrowth with a reduction in the percentage of lethal tumors observed essentially in hosts injected with inhibited IGF-I expression cells.
Assuntos
Antígenos de Superfície/metabolismo , Melanoma Experimental/metabolismo , Animais , Antibacterianos/farmacologia , Antígenos CD/genética , Antígenos CD/metabolismo , Antígenos de Superfície/genética , Antígeno B7-1/genética , Antígeno B7-1/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , DNA Antissenso/genética , Regulação para Baixo/efeitos dos fármacos , Eletroporação/métodos , Feminino , Citometria de Fluxo , Expressão Gênica/efeitos dos fármacos , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe I/metabolismo , Higromicina B/farmacologia , Imuno-Histoquímica , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Integrina alfa4/genética , Integrina alfa4/metabolismo , Melanoma Experimental/genética , Melanoma Experimental/patologia , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Ovalbumina/genética , Ovalbumina/metabolismo , Tetraspanina 28 , Tetraspanina 29 , Transfecção/métodosRESUMO
Class 1 major histocompatibility complex (MHC-I)-antigenic peptide exposed at the target cell surface is crucial for the adaptive immune response exerted in the self/syngeneic context by cytotoxic T lymphocyte (CTL). Such a complex also provides epitopes in the allogeneic context for antibody response directed against the MHC-I polymorphic determinant. In the present report we examined the formation of the MHC-I-peptide complex leading predominantly to the expression of T and/or B cell epitopes in a process of internal versus external antigenic peptide loading onto the binding groove of MHC-I. Analyses using antibodies specific to complex MHC-I-peptide generated in the syngeneic context to mimic T cell receptor (TCR) in comparison with antibodies specific to the MHC-I polymorphic determinant allowed the observation that the external peptide loading to MHC-I, while remaining necessary for inducing the formation of B cell epitopes, was less efficient than the internal one for generating T cell epitopes. Thus, external loading of peptide to the MHC-I appeared to match more closely the allogeneic situation and the humoral immunity in general, while internal peptide loading corresponded with the self/syngeneic context of the cellular CTL response.