Volume 25 Issue 1, January 2025

In this Comment, Connor et al. discuss how the continued poor clinical translatability of preclinical studies highlights the need to mandate well-characterized models, ideally established in the orthotopic setting and, where feasible, treated with classical standard-of-care regimens.

Wang et al. demonstrate that lactate derived from glioblastoma stem cells, microglia and macrophages drives histone lactylation, activating immunosuppressive transcriptional programs and upregulating CD47, to suppress phagocytosis.

Intercellular mitochondrial transfer via tunnelling nanotubes can influence cellular bioenergetics and function in tumours. A study in Cell demonstrates how this process can increase CD8⁺ T cell metabolic fitness and anti-tumour function.

In this Journal Club, Sabarinathan discusses a study suggesting immunoproteasome expression as a potential biomarker of response to immune checkpoint inhibition in melanoma.

Single-cell epigenomic technologies are refining our understanding of cancer evolution. Here Laisné et al. describe how epigenomic heterogeneity generates dynamic reservoirs of tumour cell states, through epigenomic reprogramming and selection among stochastic changes, which can be leveraged in the design of novel therapies.

Immunotherapy shows promise in treating cancers by engineering T cells or using antibodies to activate them. However, cancer stem cells (CSCs) resist immunotherapies and drive cancer relapse. In this Review, Agudo and Miao highlight the mechanisms through which normal stem cells and CSCs in solid tumours achieve immune resistance, offering insights for the development of more effective cancer treatments.

In this Review, Hanahan et al. discuss how, in response to tumorigenesis, nearly all cell types in the tumour microenvironment can be programmed to mediate — as functionally distinct subtypes — immunosuppressive programmes that result in the inhibition of antitumour T cell activity and the evasion of immune destruction.

The Cancer Dependency Map (DepMap) is a data repository and research platform that can be utilized to systematically identify cancer vulnerabilities. Here Arafeh, Shibue et al. outline the current limitations and future strategies to enhance the DepMap project.