Associations of PD-L1, PD-L2, and HLA class I expression with responses to immunotherapy in patients with advanced sarcoma: post hoc analysis of a phase 1/2 trial.

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.

Apariencia mamográfica del carcinoma in situ en pacientes del Hospital Nacional Guillermo Almenara / Appearance mammography of the carcinoma in situ in patients of the Hospital Nacional Guillermo Almenara

El objetivo del estudio fue determinar las características radiológicas del carcinoma in situ (CIS) de mama, estableciendo la relación entre los hallazgos mamográficos y tipos histológicos. Entre diciembre del 2000 y julio del 2002, se realizaron 286 localizaciones por aguja en el Servicio de Radiología del Hospital Guillermo Almenara Irigoyen en pacientes con alta sospecha de cáncer de mama, de los cuales 39 (14 por ciento) fueron confirmados histológicamente como cáncer y 15 (38,46 por ciento) carcinoma in situ. Se consideraron para el estudio además, 6 pacientes a quienes se le realizó BAAF (3) o biopsia por recisión local (3) todas ellas pacientes en que la sospecha diagnóstica de cáncer fue planteada por el medio de mamografía, haciendo un total de 21 pacientes. Los tipos de presentación mamográfico en orden de frecuencia del Ca in situ de la mama en el presente estudio fueron las microcalcificaciones solas fueron la manifestación mamográfica más frecuente 47,62 por ciento (10). En general, 17(80,95 por ciento) pacientes presentaron alguna forma de microcalcificación asociada o no a otros hallazgos como distorsión asimétrica focal, distorsión de la arquitectura. En cuanto a los tipos histológicos del carcinoma in situ, el más frecuente fue el carcinoma intraductal 90,47 por ciento (19). En conclusión, la incidencia de carcinoma in situ de la mama fue 38,46 por ciento y es ligeramente más alta a los reportes internacionales. La manifestación radiológica más frecuente del CIS fueron microcalcificaciones solas o asociadas a otro tipo de hallazgo mamográfico (80,9 por ciento), siendo así que la forma más frecuente del CIS, fueron las microcalcificaciones solas, seguidas por la distorsión asimetría focal asociada a microcalcificaciones.

Development of nuclear DNA probes for the typing of Trypanososma cruzi

We have developed and tested a new way of typing Trypanosoma cruzi, mamely the use of cloned nuclear DNA fragments as genetic markers. Restriction fragment length polymorphisms were verified on Soutern blots hybridized to random probes. Fragment patterns were analyzed and dendrograms constructed. Our results on well characterized laboratory strains correlate well to published isoenzyme studies. Some of the probes were also hybridized to chromosomes separated by pulse field gel electrophoresis a higher degree of heterogeneity was observed at this level

Development of nuclear DNA probes for the typing of Trypanosoma cruzi.

We have developed and tested a new way of typing Trypanosoma cruzi, namely the use of cloned nuclear DNA fragments as genetic markers. Restriction fragment length polymorphisms were verified on Southern blots hybridized to random probes. Fragment patterns were analyzed and dendrograms constructed. Our results on well characterized laboratory strains correlate well to published isoenzyme studies. Some of the probes were also hybridized to chromosomes separated by pulse field gel electrophoresis and a higher degree of heterogeneity was observed at this level.