Immune Exclusion Is Frequent in Small-Cell Carcinoma of the Bladder.

Small-cell cancer of the urinary bladder is a rare but highly aggressive disease. It is currently unclear whether immune checkpoint therapies that have been approved for urothelial carcinomas will also be efficient in small-cell carcinomas. In this study, we analyzed potential predictors of response including PD-L1 expression and the quantity and location of tumor-infiltrating lymphocytes (TILs) in 12 small-cell and 69 "classical" urothelial cancers by immunohistochemistry. The analysis revealed that small-cell carcinomas were characterized by the virtual absence of PD-L1 expression and an "immune-excluded" phenotype with only a few TILs in the center of the tumor (CT). In small-cell carcinomas, the average immune cell density in the CT (CD3: 159 ± 206, CD8: 87 ± 169 cells/mm2) was more than 3 times lower than that in the urothelial carcinomas (CD3: 625 ± 800, p < 0.001; CD8: 362 ± 626 cells/mm2, p = 0.004) while there was no significant difference in the immune cell density at the invasive margin (IM) (small-cell carcinomas CD3: 899 ± 733, CD8: 404 ± 433 cells/mm2; urothelial carcinomas CD3: 1167 ± 1206, p = 0.31; CD8: 582 ± 864 cells/mm2, p = 0.27). Positive PD-L1 staining was found in 39% of urothelial cancers, but in only 8% of small-cell bladder cancer cases (p = 0.04). Concordant with these data, a sharp decrease of PD-L1 positivity from >80% to 0% positive cells and of TILS in the CT from 466-1063 CD3-positive cells/mm2 to 50-109 CD3-positive cells/mm2 was observed in two cancers with clear-cut progression from "classical" urothelial to small-cell carcinoma. In conclusion, these data demonstrate that small-cell bladder cancer commonly exhibits an immune-excluded phenotype.

Exploring the value and role of integrated supportive science courses in the reformed medical curriculum iMED: a mixed methods study.

BACKGROUND: Heterogeneous basic science knowledge of medical students is an important challenge for medical education. In this study, the authors aimed at exploring the value and role of integrated supportive science (ISS) courses as a novel approach to address this challenge and to promote learning basic science concepts in medical education. ISS courses were embedded in a reformed medical curriculum. METHODS: The authors used a mixed methods approach including four focus groups involving ISS course lecturers and students (two each), and five surveys of one student cohort covering the results of regular student evaluations including the ISS courses across one study year. They conducted their study at the University Medical Center Hamburg-Eppendorf between December 2013 and July 2014. RESULTS: Fourteen first-year medical students and thirteen ISS course lecturers participated in the focus groups. The authors identified several themes focused on the temporal integration of ISS courses into the medical curriculum, the integration of ISS course contents into core curriculum contents, the value and role of ISS courses, and the courses' setting and atmosphere. The integrated course concept was positively accepted by both groups, with participants suggesting that it promotes retention of basic science knowledge. Values and roles identified by focus group participants included promotion of basic understanding of science concepts, integration of foundational and applied learning, and maximization of students' engagement and motivation. Building close links between ISS course contents and the core curriculum appeared to be crucial. Survey results confirmed qualitative findings regarding students' satisfaction, with some courses still requiring optimization. CONCLUSIONS: Integration of supportive basic science courses, traditionally rather part of premedical education, into the medical curriculum appears to be a feasible strategy to improve medical students' understanding of basic science concepts and to increase their motivation and engagement.