Cancer

Since a detailed inventory of endothelial cell (EC) heterogeneity in breast cancer (BC) is lacking, here we perform single cell RNA-sequencing of 26,515 cells (including 8433 ECs) from 9 BC patients and compare them to published EC taxonomies from lung tumors. Angiogenic ECs are phenotypically similar, while other EC subtypes are different. Predictive interactome analysis reveals known but also previously unreported receptor-ligand interactions between ECs and immune cells, suggesting an involvement of breast EC subtypes in immune responses.

Zika virus (ZIKV) can infect human developing brain (HDB) progenitors resulting in epidemic microcephaly, whereas analogous cellular tropism offers treatment potential for the adult brain cancer, glioblastoma (GBM). We compared productive ZIKV infection in HDB and GBM primary tissue explants that both contain SOX2+ neural progenitors. Strikingly, although the HDB proved uniformly vulnerable to ZIKV infection, GBM was more refractory, and this correlated with an innate immune expression signature.

Single-strand selective uracil-DNA glycosylase 1 (SMUG1) initiates base excision repair (BER) of uracil and oxidized pyrimidines. SMUG1 status has been associated with cancer risk and therapeutic response in breast carcinomas and other cancer types. However, SMUG1 is a multifunctional protein involved, not only, in BER but also in RNA quality control, and its function in cancer cells is unclear. Here we identify several novel SMUG1 interaction partners that functions in many biological processes relevant for cancer development and treatment response.

T cell receptor (TCR)-based immunotherapy has emerged as a promising therapeutic approach for the treatment of patients with solid cancers. Identifying peptide-human leukocyte antigen (pHLA) complexes highly presented on tumors and rarely expressed on healthy tissue in combination with high-affinity TCRs that when introduced into T cells can redirect T cells to eliminate tumor but not healthy tissue is a key requirement for safe and efficacious TCR-based therapies.

Background Despite recent approval of anti-PD-1 antibodies as 1L therapy in advanced GEA, benefit is largely limited to PD-L1 combined positive scores (CPS) ≥5 patients (pts); novel therapeutic approaches are needed. DKN-01 is a targeted anti-DKK1 mAb which has demonstrated activity in GEA pts with elevated tumoral DKK1 expression, a subset of pts with more aggressive disease and shorter overall survival. Methods Phase IIa single arm trial investigating DKN-01 300 mg (D) + tislelizumab (TS) + CAPOX as 1L therapy in advanced HER2(-) GEA regardless of DKK1 status.

Although melanoma is notorious for its high degree of heterogeneity and plasticity1,2, the origin and magnitude of cell-state diversity remains poorly understood. Equally, it is unclear whether growth and metastatic dissemination are supported by overlapping or distinct melanoma subpopulations.

Abstract Unavailable

Nasopharyngeal carcinoma (NPC) is generally regarded as a genetic disease with diverse extent of intertumor and intratumor heterogeneity. Here we propose that, NPC is not only a genetic disease; it could be conceptualized as a multidimensional spatiotemporal “unity of ecology and evolution” pathological ecosystem.

RNA sequencing of unclassified soft tissue tumors has allowed for definition of multiple new entities. Antonescu et al. recently reported three case of low grade sarcoma with recurrent EWSR1/FUS::NACC1 fusion and distinctive storiform architecture that were suggestive of a novel tumor type.Here, we present a case of an additional sarcoma with FUS::NACC1 fusion that arose in the head and neck and showed immunohistochemical evidence of epithelial differentiation.A 41 year old woman presented with throat and inner ear pain and was found to have a nasopharyngeal mass.