RESUMO
We present a case of a patient with metastatic nasopharyngeal carcinoma who failed two lines of palliative combination chemotherapy and was treated with allogeneic nonmyeloablative stem cell transplantation (NST). This patient achieved a durable tumor response, dramatic relief of his symptoms, and elimination of tumor in his bone marrow-an effect likely achieved via a graft-versus-tumor response. Although NST has been explored previously in solid tumors, such as renal cell carcinoma and breast cancer, it has not been widely explored in nasopharyngeal carcinoma. We also present data from a flow cytometric immune analysis and cytokine enzyme-linked immunosorbent assay analysis in the pre- and post-NST period.
Assuntos
Efeito Enxerto vs Tumor , Neoplasias Nasofaríngeas , Transplante de Células-Tronco , Neoplasias da Medula Óssea/secundário , Carcinoma , Quimioterapia Combinada/efeitos adversos , ELISPOT , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/terapia , Metástase Neoplásica/terapia , Cuidados Paliativos , Transplante HomólogoRESUMO
G-CSF can induce functional immune tolerance in man. In this study, purified T cells from G-CSF-mobilized peripheral blood stem cell (PBSC) donors were analysed by gene expression profiling and immunophenotyping. Results suggested a predominantly immune tolerant profile with upregulation of genes related to Th2 and Treg cells, downregulation of genes associated with Th1 cells, cytotoxicity, antigen presentation and graft-versus-host disease (GVHD) and overexpression of negative regulators of Th17 differentiation. Immunophenotyping revealed that during G-CSF exposure donors had reduced levels of T cells with a Th17 phenotype (CD4+IL-17A+CCR6+IL-23R+), more than three times lower compared to normal controls. G-CSF also led to increased levels of CD4+CD25highCD45RO+ Treg cells. Furthermore, mRNA levels of RORgammat, a Th17-specific transcription factor, decreased in T cells isolated from G-CSF-mobilized PBSC harvests. Th17 cells have been implicated in autoimmune diseases and GVHD pathophysiology. Our study is the first to report the effect of G-CSF on the Th17 subpopulation.