Volume 5 Issue 2, February 2024

A genome-wide study of variation in mutation rates in human cancer reveals robust patterns of change in mutation risk across chromosomal domains and with varying replication times.

Cancer cells seed distant tissues and remain dormant before re-entering the cell cycle to form metastases. How tumor dormancy is maintained and how cells exit dormancy is poorly understood. A study shows that the lncRNA MALAT1 reactivates dormant cancer cells by upregulating serpin protease inhibitors in tumor cells to evade CD8⁺ T cells.

Autotaxin (ATX) produces lysophosphatidic acid (LPA), which directly promotes pancreatic ductal adenocarcinoma (PDAC) growth, but the role of the tumor microenvironment (TME) in ATX-driven tumor growth is unclear. ATX–LPA signaling in PDAC is now shown to shape the TME by inhibiting eosinophil recruitment, resulting in increased tumor growth.

We developed a method for generating dendritic cell progenitors (DCPs) from hematopoietic stem and progenitor cells isolated from bone marrow or blood. When engineered to express IL-12 and FLT3L, these DCPs reprogram the tumor microenvironment and elicit anti-tumor immunity without the need for ex vivo antigen loading.

We applied an artificial intelligence (AI) approach to a dataset of clinical and advanced multi-omic molecular features from patients with pancreatic adenocarcinoma to predict survival. The results reveal a tumor-type-agnostic platform that can identify parsimonious and robust clinical prediction biomarkers, catalyzing the vision to democratize precision oncology worldwide.

Van Loo and colleagues review the mechanistic underpinnings of large genomic alterations and their roles in tumor development and evolution.

De Palma and colleagues develop a dendritic cell therapy based on dendritic cell progenitors engineered to produce IL-12 and FLT3L and show antigen-agnostic reduction of tumor burden that can be exploited for combination therapy in glioma.

Kumar et al. show that the lncRNA Malat1 prevents gasdermin D-mediated pyroptosis induction, in turn suppressing inflammatory cell death and mediating immune evasion and metastasis.

Sherman and colleagues show that ATX suppresses the accumulation of eosinophils in the tumor microenvironment of pancreatic cancer via suppression of CCL11 expression and find that ATX inhibition increases eosinophil influx, promoting tumor cell death.

Theodorescu and colleagues describe a Molecular Twin approach that integrates multi-omic and computational pathology data from patients with pancreatic ductal adenocarcinoma using artificial intelligence to predict clinical outcomes.

Leibold and colleagues develop a method to somatically introduce oncogenic lesions into the stomach epithelium, which recapitulates the histological, molecular and clinical features of human gastric cancer.

Salvadores and Supek derive three regional mutation density signatures from whole-genome profiles of >4,000 tumors that are associated with cell cycle gene expression and alter somatic mutation rates independently of tissue of origin.

Yuan and colleagues developed an artificial intelligence-based method to derive growth patterns and morphological features from hematoxylin and eosin-stained slides of lung adenocarcinoma samples, for improved tumor grading and patient prognostication.