Spatial predictors of immunotherapy response in triple-negative breast cancer.

Immune checkpoint blockade (ICB) benefits some patients with triple-negative breast cancer, but what distinguishes responders from non-responders is unclear1. Because ICB targets cell-cell interactions2, we investigated the impact of multicellular spatial organization on response, and explored how ICB remodels the tumour microenvironment. We show that cell phenotype, activation state and spatial location are intimately linked, influence ICB effect and differ in sensitive versus resistant tumours early on-treatment. We used imaging mass cytometry3 to profile the in situ expression of 43 proteins in tumours from patients in a randomized trial of neoadjuvant ICB, sampled at three timepoints (baseline, n = 243; early on-treatment, n = 207; post-treatment, n = 210). Multivariate modelling showed that the fractions of proliferating CD8+TCF1+T cells and MHCII+ cancer cells were dominant predictors of response, followed by cancer-immune interactions with B cells and granzyme B+ T cells. On-treatment, responsive tumours contained abundant granzyme B+ T cells, whereas resistant tumours were characterized by CD15+ cancer cells. Response was best predicted by combining tissue features before and on-treatment, pointing to a role for early biopsies in guiding adaptive therapy. Our findings show that multicellular spatial organization is a major determinant of ICB effect and suggest that its systematic enumeration in situ could help realize precision immuno-oncology.

Partial hydatidiform mole and coexistent live fetus with placenta previa: a case report.

Partial molar pregnancy with a coexistent live fetus is very rare. This type of mole mostly ends in the early termination of pregnancy due to an abnormally developed fetus. Case presentation: Here, we report a case of a 24-year-old Indonesian woman with an ultrasonographic appearance of partial hydatidiform mole with initial placenta covering the internal uterine ostium in the late first trimester which then became marginal placenta previa in the third trimester. The woman decided to continue the pregnancy after considering the risks and benefits. The normal anatomy of the premature infant was vaginally delivered alive with a large and hydropic placenta. Clinical discussion: Proper diagnosis, management, and monitoring remain challenging as this case is still rarely reported. Although embryos from partial mole forms generally do not survive since the first trimester, our case reported the singleton pregnancy with the coexistent normal fetus and the partial mole characteristic of the placenta. Diploid karyotype, few and focal extent of hydatidiform tissue of placenta, low rate of molar degeneration, and the absence of fetal anemia hypothesized as the factors that influenced survival of the fetus. There were two maternal complications such as hyperthyroidism and frequent vaginal bleeding without subsequent anemia in this patient. Conclusions: A rare case of partial hydatidiform mole coexistent with a live fetus with placenta previa was reported in this study. There were also maternal complications. Thus, prompt and regular monitoring of maternal and fetal condition holds an important role.