News & Comment

Ostendorf et al. show that germline variants of human APOE play a role in melanoma that is opposite to that in Alzheimer disease, with APOE4 carrier status being associated with reduced melanoma growth in mice and improved outcome in patients with advanced melanoma.

The COVID-19 pandemic has broadly impacted biomedical research and health care. Here we discuss current challenges for the cancer research community as they apply to early career investigators (ECIs). We propose a series of collaborative initiatives aimed to sustain ECIs and preserve and accelerate the ability to innovate with long-lasting impact.

Ting Li, Xinyuan Li et al. determined that REL, a member of the nuclear factor-κB (NF-κB) family of transcription factors, has a key role in generating myeloid-derived suppressor cells (MDSCs) and that targeting REL might be used for cancer immunotherapy.

Normal tissues become colonized by clones, which have acquired somatic mutations in common cancer driver genes. Colom et al. have now shown that the fate of mutagen-exposed oesophageal epithelial cells in mice is governed by the genotype of their neighbours with implications for cancer development.

In conflict-affected areas, people experience significant challenges in health-care delivery, and this situation is even more extreme for patients with cancer. Until now, research on access to cancer treatment and care as well as cancer disparities in war-torn and post-war regions has been limited. Therefore, we advocate coordinated, global action to address this issue and implement evidence-based solutions.

Morral, Stanisavljevic et al. show that colorectal cancer (CRC) cell hierarchy is based on the capacity to perform biosynthesis. Undifferentiated CRC cells that have high capacity for protein synthesis were found immediately adjacent to the stroma, and this capacity was lost upon differentiation.

Chung et al. studied drivers of obesity-associated pancreatic ductal adenocarcinoma in a leptin-deficient mouse model and identified the hormone cholecystokinin, upregulated in islet beta cells in the context of obesity, to be promoting pancreatic tumorigenesis.

The group of Sangeeta Bhatia have leveraged a set of nanosensors to diagnose lung cancer in mice by detecting and amplifying the activity of dysregulated extracellular proteases, offering a urine-based readout.

Roulis, Kaklamanos et al. have identified a population of rare fibroblasts present in intestinal crypts that promote intestinal tumorigenesis in a paracrine manner through prostaglandin E2 signalling.

Klichinsky et al. have engineered macrophages to express chimeric antigen receptors (CARs) that target their phagocytic activity towards tumour cells. These macrophages (CAR-Ms) reduced tumour burden and prolonged overall survival in mice.

Two recent papers have investigated the potential roles that changes in chromosome numbers might have on the evolution and progression of tumours.

Hoekstra et al. and Thibaut et al., both reporting in Nature Cancer, show that interferon-γ secreted by tumour-reactive T cells diffuses into the tumour microenvironment and acts on remote tumour cells to modify tumour behaviour.

Pleguezuelos-Manzano et al. have discovered a mutational signature in colorectal cancer that arises following exposure to genotoxic pks⁺ E. coli, firmly establishing causality.

Two studies by Park et al. and Papalarazou et al. explored mechanoresponses of cancer cell metabolism in the lung and pancreas, respectively. They identify distinct mechanisms of adaptation to changes in extracellular matrix stiffness, thereby maintaining the cells’ ability to grow or disseminate.

Yoshida, Gowers et al. examined somatic mutations in normal lung epithelium to better understand the effects of tobacco smoking, and stopping smoking, on normal tissue biology and how these effects relate to lung cancer development.

Zagato et al. have identified bacterial species of the microbiome that are lost during intestinal tumorigenesis. Mouse Faecalibaculum rodentium and its human homologue exert their antitumorigenic effect on cell proliferation through the production of short chain fatty acids.

Ajona et al. have shown that short-term starvation can sensitize lung tumours in mice to the action of immune checkpoint blockade through a reduction in levels of circulating insulin-like growth factor 1 (IGF1).

A recent study from Ralph DeBerardinis’ and Sean Morrison’s labs has found that metastatic melanoma cells upregulate the lactate transporter MCT1 in vivo to manage oxidative stress, which allows them to survive during dissemination.

Sinha et al. systematically mapped genomic alterations in lung tumours from an ethnically unbiased patient cohort and demonstrated a higher frequency of homologous recombination deficiency in tumours from African Americans than European Americans, highlighting the need to include diverse populations in cancer genomics studies.

Jansen et al. show in patients with cancer that intratumoural stem-like CD8⁺ T cells reside in antigen-presenting cell (APC) niches in the tumour and give rise to terminally differentiated T cells.