Research Highlights in 2022

In a study in Nature, Wang et al. describe how circadian rhythms can impact tumour suppression through their effects on dendritic cells, a finding that could help to optimize clinical trials of cancer immunotherapies.

Two recent studies have demonstrated how senescent cancer cells alter their cell surface proteome to induce anti-tumour immune responses, highlighting the potential therapeutic role of inducing senescence to improve anti-tumour immunity.

In this study, Cao et al. identified previously undiscovered metabolites produced by human gut microbes that cause DNA damage, and analysed their implication for colorectal cancer development.

Schmitt et al. describe an adaptive mechanism employed by colorectal cancers to handle pro-apoptotic chemotherapeutic insults, which could represent a targetable vulnerability with combination therapy.

Notarangelo et al. reveal that the oncometabolite d-2-hydroxyglutarate, which is released in high quantities by tumour cells, is taken up by CD8⁺ T cells in the tumour microenvironment and blocks their proliferation and cytotoxicity by inhibition of lactate dehydrogenase and metabolic reprogramming.

In two studies published concurrently, Dohlman et al. and Narunsky-Haziza et al. have found strong correlative links between the prevalence of fungal DNA and cancer.

Karras et al. map cell state diversity in melanoma and identify a cellular hierarchy that is regulated by microenvironmental cues.

Kalkavan et al. find sublethal cytochrome c release leads to a caspase-independent, ATF4-dependent drug-tolerant persister phenotype.

Using single-cell RNA-seq and functional analysis in prostate cancer organoids and mouse models, Chan et al. identify inflammatory JAK–STAT signalling to drive the transition of adenocarcinomas to neuroendocrine prostate cancer.

Ma et al. demonstrate that platelets suppress liver tumour growth in the context of non-alcoholic fatty liver disease through T cell-dependent antitumour immunity.

Xu, Yan et al. show that the hypothalamic–pituitary unit produces α-melanocyte-stimulating hormone in tumour-bearing mice, to promote myelopoiesis and immunosuppression.

Using a reporter system in a mouse model of pancreatic cancer, Baslan et al. detail the progression of genomic disruption following p53 loss.

In two studies published concurrently, Pal et al. and Shi et al. reveal that certain gliomas rely on the de novo synthesis of pyrimidines. These studies go on to demonstrate the effectiveness of brain-penetrant inhibitors of de novo pyrimidine synthesis in preclinical models of glioma.

Chen et al. have developed a preclinical platform that enables the reprogramming of locoregional macrophages and microglia in situ with CD133-directed chimeric antigen receptors, which leads to the phagocytosis and removal of residual glioma stem cells after tumour debulking.

Barkley and colleagues conducted single-cell RNA sequencing of almost 20,000 malignant cells and identified cancer cell states that are both common and different across tumour types, and revealed how these states interact with the tumour microenvironment.

Seki et al. show that exposure to cold suppresses tumour growth in mice through increasing glucose uptake and thermogenesis in brown adipose tissue.

Venkataramani et al. used longitudinal intravital two-photon imaging to track migrating glioblastoma cells in vivo, and identified a seemingly unconnected cell subpopulation that was responsible for colonization of the brain by mimicking neuronal mechanisms of movement.

Using single-cell transcriptomic data, Joanito et al. reveal that colorectal cancers can be defined by the presence of one of two major intrinsic epithelial subtypes, and present a refined molecular classification system for these cancers.

Finding sex differences in the response of patients with melanoma to BRAF/MEK-targeted therapy, Vellano et al. show that this effect is mediated by androgen receptor expression and demonstrate that androgen receptor blockers can enhance treatment response.