RESUMEN
PURPOSE: The establishment of a preclinical model of the abscopal effect on hepatocellular carcinoma (HCC) and evaluation of whether the hypofractionated radiation therapy (RT) multitumor Hepa1-6 mouse HCC model could be used to suppress nonradiated tumor mass was performed in this study. METHODS AND MATERIALS: Hepa1-6 mouse liver cancer cell lines were used to form tumors. Immunogenicity was analyzed using ELISpot and immune cell labeled antibody. Interferon (IFN) ß expression was confirmed through polymerase chain reaction. RESULTS: After investigation, the intratumoral transcription of type â IFN increased by 2-fold. The antitumor immune response to Hepa 1-6 cells induced by radiation was increased. Moreover, the influx of activated CD8+ T cells was increased in nonirradiated tumors. The number of dendritic cells and activation status were evaluated by flow cytometry on the second day after irradiation. Flow cytometry revealed a significantly increased dendritic cell population expressing the CD11c molecule in tumor-draining lymph nodes. Furthermore, because irradiation leads to adaptation of immune resistance of tumor cells against RT, we sought to elucidate a potent tool to overcome the resistance and confirm the ability of PD-L1 antibody to survive late RT resistance. CONCLUSIONS: The immunologic mechanism of the abscopal effect was revealed and the application of PD-L1 inhibitor successfully performed as a breakthrough in late RT resistance in the Hepa1-6 tumor model.
Asunto(s)
Carcinoma Hepatocelular/terapia , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Hepáticas/terapia , Tolerancia a Radiación/inmunología , Radiocirugia/métodos , Animales , Antineoplásicos , Antígeno B7-H1/administración & dosificación , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/metabolismo , Antígenos CD11/metabolismo , Linfocitos T CD8-positivos/citología , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/efectos de la radiación , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Terapia Combinada/métodos , Células Dendríticas/citología , Células Dendríticas/inmunología , Células Dendríticas/efectos de la radiación , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Femenino , Citometría de Flujo , Interferón Tipo I/metabolismo , Interferón beta/metabolismo , Interferón gamma/inmunología , Interferón gamma/metabolismo , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/patología , Ganglios Linfáticos/metabolismo , Linfocitos Infiltrantes de Tumor/citología , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/efectos de la radiación , Ratones , Ratones Endogámicos C57BL , Trasplante de Neoplasias , Hipofraccionamiento de la Dosis de Radiación , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Carga Tumoral/efectos de la radiaciónRESUMEN
Neuroendocrine tumor (NET) of the major duodenal papilla is a rare occurrence. However, that of the minor duodenal papilla is even rarer. To date, only a few cases have been reported. Herein, we present a rare case of NETs detected at the major and minor duodenal papilla synchronously, which were successfully treated with endoscopic papillectomy without procedure-related complication. To the best of our knowledge, this is the first report of this kind in the world. Photomicrograph of the biopsy specimen stained immunohistochemically for synaptophysin showed a positive reaction of tumor cells. All resection margins were negative. Further experience with more cases will be needed to establish the exact indication of endoscopic papillectomy for duodenal papillary NETs.