ABSTRACT
Transition support is an integral part of the care of adolescents in clinical services. To avoid disruptions in the care pathway, transition spaces in pediatric and adult hospitals are emerging. There are currently fifteen in France. The professionals working there and the tools and methods used are heterogeneous, but with a common challenge which is the reduction of the major risk of disruption of the care pathway and support for the life course.
Subject(s)
Transition to Adult Care , Adult , Humans , Child , Adolescent , Hospitals , FranceABSTRACT
Single cell technologies allow the interrogation of tumor heterogeneity, providing insights into tumor evolution and treatment resistance. To better understand whether circulating tumor cells (CTCs) could complement metastatic biopsies for tumor genomic profiling, we characterized 11 single CTCs and 10 pooled CTC samples at the mutational and copy number aberration (CNA) levels, and compared these results with matched synchronous tumor biopsies from 3 metastatic breast cancer patients with triple-negative (TNBC), HER2-positive and estrogen receptor-positive (ER+) tumors. Similar CNA profiles and the same patient-specific driver mutations were found in bulk tissue and CTCs for the HER2-positive and TNBC tumors, whereas different CNA profiles and driver mutations were identified for the ER+ tumor, which presented two distinct clones in CTCs defined by mutations in ESR1 Y537N and TP53, respectively. Furthermore, de novo mutational signatures derived from CTCs described patient-specific biological processes. These data suggest that tumor tissue and CTCs provide complementary clinically relevant information to map tumor heterogeneity and tumor evolution.
ABSTRACT
BACKGROUND: Recent efforts of gene expression profiling analyses recognized at least four different triple-negative breast cancer (TNBC) molecular subtypes. However, little is known regarding their tumor microenvironment (TME) heterogeneity. METHODS: Here, we investigated TME heterogeneity within each TNBC molecular subtype, including immune infiltrate localization and composition together with expression of targetable immune pathways, using publicly available transcriptomic and genomic datasets from a large TNBC series totaling 1512 samples. Associations between molecular subtypes and specific features were assessed using logistic regression models. All statistical tests were two-sided. RESULTS: We demonstrated that each TNBC molecular subtype exhibits distinct TME profiles associated with specific immune, vascularization, stroma, and metabolism biological processes together with specific immune composition and localization. The immunomodulatory subtype was associated with the highest expression of adaptive immune-related gene signatures and a fully inflamed spatial pattern appearing to be the optimal candidate for immune check point inhibitors. In contrast, most mesenchymal stem-like and luminal androgen receptor tumors showed an immunosuppressive phenotype as witnessed by high expression levels of stromal signatures. Basal-like, luminal androgen receptor, and mesenchymal subtypes exhibited an immune cold phenotype associated with stromal and metabolism TME signatures and enriched in margin-restricted spatial pattern. Tumors with high chromosomal instability and copy number loss in the chromosome 5q and 15q regions, including genomic loss of major histocompatibility complex related genes, showed reduced cytotoxic activity as a plausible immune escape mechanism. CONCLUSIONS: Our results demonstrate that each TNBC subtype is associated with specific TME profiles, setting the ground for a rationale tailoring of immunotherapy in TNBC patients.