RESUMEN
BACKGROUND: Although immunotherapy is thought to be a promising cancer treatment, most patients do not respond to immunotherapy. In this post hoc analysis of a phase 1/2 study, associations of programmed death ligand 1 (PD-L1), PD-L2, and HLA class I expressions with responses to dendritic cells (DCs)-based immunotherapy were investigated in patients with advanced sarcoma. METHODS: This study enrolled 35 patients with metastatic and/or recurrent sarcomas who underwent DC-based immunotherapy. The associations of PD-L1, PD-L2, and HLA class I expressions in tumor specimens, which were resected before immunotherapy, with immune responses (increases of IFN-γ and IL-12) and oncological outcomes were evaluated. RESULTS: Patients who were PD-L2 (+) showed lower increases of IFN-γ and IL-12 after DC-based immunotherapy than patients who were PD-L2 (-). The disease control (partial response or stable disease) rates of patients who were PD-L1 (+) and PD-L1 (-) were 0% and 22%, respectively. Disease control rates of patients who were PD-L2 (+) and PD-L2 (-) were 13% and 22%, respectively. Patients who were PD-L1 (+) tumors had significantly poorer overall survival compared with patients who were PD-L1 (-). No associations of HLA class I expression with the immune response or oncological outcomes were observed. CONCLUSIONS: This study suggests that PD-L1 and PD-L2 are promising biomarkers of DC-based immunotherapy, and that addition of immune checkpoint inhibitors to DC-based immunotherapy may improve the outcomes of DC-based immunotherapy.
Asunto(s)
Antígeno B7-H1/metabolismo , Antígenos de Histocompatibilidad Clase I/metabolismo , Inmunoterapia , Proteína 2 Ligando de Muerte Celular Programada 1/metabolismo , Sarcoma/terapia , Adulto , Biomarcadores de Tumor/metabolismo , Células Dendríticas , Femenino , Humanos , Interferón gamma/metabolismo , Interleucina-12/metabolismo , Masculino , Sarcoma/inmunología , Sarcoma/mortalidad , Sarcoma/patología , Resultado del TratamientoRESUMEN
We detected primary human herpesvirus 6 (HHV-6) infection in 5 infants who received living related liver transplantation from their HHV-6 seropositive mothers. Primary HHV-6 infection was confirmed by demonstrating the seroconversion of HHV-6 antibodies with an immunofluorescence assay, by the isolation of the virus, or both. Seroconversion of HHV-6 immunoglobulin G antibody was demonstrated in all 5 recipients. HHV-6 was isolated from 3 of the 5 recipients between 2 and 3 weeks after transplantation. Moreover, the virus genome was detected in plasma by polymerase chain reaction in 4 of the 5 recipients during the same period. Although the 5 recipients had pyrexia at the time of primary HHV-6 infection, none of the recipients had a skin rash after defervescence. Clinical symptoms disappeared without specific antiviral treatment in all but 1 of the recipients.
Asunto(s)
Infecciones por Herpesviridae/transmisión , Herpesvirus Humano 6 , Trasplante de Hígado , ADN Viral/sangre , Femenino , Herpesvirus Humano 6/aislamiento & purificación , Humanos , Lactante , Masculino , Complicaciones Posoperatorias , Donantes de TejidosRESUMEN
The degree of viremia with human herpesvirus-6 was evaluated in 176 blood samples from 89 infants with exanthem subitum and viremia, and compared with the severity of clinical features and complications of the disease. Fever persisted for 3 to 4 days in 73% of infants and for more than 5 days in 22%, followed by a rubella- or measles-like rash. The viremia was observed between the first day of fever (day 0) and day 4 of the disease. The number of infected cells per 10 million mononuclear cells was 3.45 +/- 1.00 (log10, mean +/- SD) on days 0 to 2, 3.30 +/- 1.14 on day 3, and 3.09 +/- 2.05 on day 4 of the disease. The number of infected cells on days 3 to 4 in infants with a febrile period longer than 4 days and free virus in plasma was significantly greater than that in infants with a febrile period of less than 3 days and without free virus in plasma. The amount of virus in blood on days 0 to 2 did not relate to the duration of fever, and that on days 0 to 4 did not relate to the presence or absence of diarrhea, bulging fontanelle, or bronchopneumonia. These findings suggest that the magnitude of the virus replication in infants with exanthem subitum is reflected in the severity of the disease.
Asunto(s)
Exantema Súbito/microbiología , Infecciones por Herpesviridae/microbiología , Herpesvirus Humano 6/aislamiento & purificación , Viremia/microbiología , Exantema Súbito/complicaciones , Femenino , Infecciones por Herpesviridae/complicaciones , Humanos , Lactante , Masculino , Índice de Severidad de la Enfermedad , Viremia/complicacionesAsunto(s)
Exantema Súbito/diagnóstico , Infecciones por Herpesviridae/diagnóstico , Exantema Súbito/complicaciones , Fiebre/etiología , Herpesviridae/aislamiento & purificación , Herpesviridae/ultraestructura , Infecciones por Herpesviridae/complicaciones , Humanos , Lactante , Leucocitos Mononucleares/microbiología , Leucocitos Mononucleares/patología , MasculinoRESUMEN
Mononuclear cell-associated viremia caused by human herpesvirus type 6 was detected in 39 (66%) of 59 blood samples from 38 children with exanthem subitum between day 0 and day 7 of the disease. The rate of virus isolation from mononuclear cells was 100% (26/26) on days 0 to 2 (just before appearance of skin rash), 82% (9/11) on day 3, 20% (2/10) on day 4, 7% (2/12) on days 5 to 7, and 0% (0/37) on day 8 and thereafter. The cell-free virus was detected in blood in 10 (21%) of 47 blood samples during the same period. The antibody activity to the virus, evaluated by a newly developed neutralization assay, was first detected on day 3 of the disease with a positive rate of 18% (2/11). It became 60% (6/10) on day 4, 75% (9/12) on days 5 to 7, and 100% on day 8 and thereafter. Thus the disappearance of the virus from blood was associated with the induction of specific immunity to the virus.