Jonathan Mannion

Hallmarks of cancer—Then and now, and beyond Hanahan revisits the evolving framework of cancer hallmarks, synthesizing 25 years of conceptual refinement into a multidimensional view of tumor biology. This review highlights how aberrant capabilities, enabling traits, microenvironmental players, and systemic interactions converge to drive tumorigenesis and proposes that mechanism-guided co-targeting of hallmarks may offer promising therapeutic strategies.

Now online! Hallmarks of cancer—Then and now, and beyond

Environmentally driven immune imprinting protects against allergy - Nature In a mouse model, environmental immunostimulation in early life led to cross-reactive adaptive immune memory and reduced type II immune responses to allergens, indicating a mechanistic relationship be...

‘Environmentally driven immune imprinting protects against allergy’

www.nature.com/articles/s41...

Molecular, Cellular, Tissue, and Organismal Functions of Type III Interferons Type III interferons are essential immune mediators playing pleiotropic roles during health and disease. In this review, we highlight the molecular and cellular pathways that lead to the production of...

💥New paper alert!💥 What’s better than starting 2026 with an @annualreviews.bsky.social #Immunology, often a once-in-a-life honor ❤️?! Check it out if you want to know everything about type III interferons #IFN! Thanks to my wonderful team for their amazing work 🤗 doi.org/10.1146/annu...

Mitotic errors as triggers of cell death and inflammation - Nature Cell Biology Rizzotto et al. discuss the causes and consequences of deregulated mitosis that allow cells arrested in mitosis to escape to the next interphase, where they can initiate inflammatory signalling or und...

Excited to announce a new review article that Andreas Villunger @villungerlab.bsky.social, Dario Rizzotto (not on bsky) and I wrote. In this article, we discuss mitosis as a central cell cycle stage for integrating DNA damage, cell death and inflammatory responses. www.nature.com/articles/s41...

Thank you very much!

Last week I was privileged to attend the @britsocimm.bsky.social 2025. The congress was packed with exciting immunology updates from around the world 🌍

I was honoured to receive a 1st place prize for my bright sparks talk ‘harnessing immunogenic cell death to improve cancer therapy’ 🏆

Lymphotoxin alpha eradicates acute myeloid leukemia and simultaneously promotes healthy hematopoiesis in mice Lymphotoxin alpha represses acute myeloid leukemia by depleting TRAF2 and triggering cell death and myeloid differentiation.

‘Lymphotoxin alpha eradicates acute myeloid leukemia and simultaneously promotes healthy hematopoiesis in mice’

www.science.org/doi/10.1126/...

After completing my PhD last Oct, I recently graduated from the @icr.ac.uk at the beautiful guildhall. An incredibly proud moment!!

A cGAS-mediated mechanism in naked mole-rats potentiates DNA repair and delays aging Efficient DNA repair might make possible the longevity of naked mole-rats. However, whether they have distinctive mechanisms to optimize functions of DNA repair suppressors is unclear. We find that na...

‘A cGAS-mediated mechanism in naked mole-rats potentiates DNA repair and delays aging’

www.science.org/doi/10.1126/...

‘RIPK1 autophosphorylation at S161 mediates cell death and inflammation’

rupress.org/jem/article/...

Linear ubiquitination prevents lipodystrophy and obesity-associated metabolic syndrome LUBAC preserves adipose tissue integrity via cell death inhibition, preventing metabolic disorders during aging and obesity.

‘Linear ubiquitination prevents lipodystrophy and obesity-associated metabolic syndrome’ 👏🏻

www.science.org/doi/10.1126/...

Obesity increases the risk of many cancers, but which fats are bad in high fat diets?
[1/3]
Lard, beef tallow or butter 🧈: ⤴️tumor growth
coconut oil 🥥, palm oil 🌴, olive oil 🫒 do not
despite equivalent obesity
www.nature.com/articles/s42...
@natmetabolism.nature.com

Humoral determinants of checkpoint immunotherapy - Nature Rapid extracellular antibody profiling reveals a contribution of autoantibodies to the effectiveness of checkpoint immunotherapy for cancer.

‘Humoral determinants of checkpoint immunotherapy’

www.nature.com/articles/s41...

Regulation of inflammatory processes by caspases - Nature Reviews Molecular Cell Biology Mammalian caspases are a group of cysteine proteases historically categorized into an ‘inflammatory’ subgroup and an ‘apoptotic’ subgroup, although accumulating evidence indicates that this distinctio...

‘Regulation of inflammatory processes by caspases’ 🔥

www.nature.com/articles/s41...

The IL-22–oncostatin M axis promotes intestinal inflammation and tumorigenesis - Nature Immunology Hegazy and colleagues demonstrate that epithelial oncostatin M receptor expression drives gut inflammation and tumor formation.

‘The IL-22–oncostatin M axis promotes intestinal inflammation and tumorigenesis’

www.nature.com/articles/s41...

VDAC2 loss elicits tumour destruction and inflammation for cancer therapy - Nature VDAC2 deficiency elicits uncontrolled IFNγ-induced BAK activation and mitochondrial damage for improved cancer therapy.

‘VDAC2 loss elicits tumour destruction and inflammation for cancer therapy’

www.nature.com/articles/s41...

STAT5 and STAT3 balance shapes dendritic cell function and tumour immunity - Nature Immune checkpoint blockade activates T cell immunity by reprogramming the STAT3 and STAT5 transcriptional pathways in dendritic cells, and STAT3 degradation is effective for treating tumours...

‘STAT5 and STAT3 balance shapes dendritic cell function and tumour immunity’

www.nature.com/articles/s41...

The E3 ubiquitin ligase complex SIFI has a role in terminating stress response signalling, to restore cellular homeostasis. Researchers @nature present the cryo-EM structure of this ~1.3 MDa complex providing insights into its mechanism of action. www.nature.com/articles/s41...

Cell type–specific efferocytosis determines functional plasticity of alveolar macrophages MPO activates an immunometabolic rheostat to restrict the functional plasticity of macrophages in favor of proresolving properties.

‘Cell type–specific efferocytosis determines functional plasticity of alveolar macrophages’

www.science.org/doi/10.1126/...

B cells modulate lung antiviral inflammatory responses via the neurotransmitter acetylcholine - Nature Immunology Cembellin-Prieto and colleagues find that B cells in the lung are capable of producing acetylcholine and that these regulate early macrophage activation and control influenza virus replication.

‘B cells modulate lung antiviral inflammatory responses via the neurotransmitter acetylcholine’ 🦠

www.nature.com/articles/s41...

Cytosolic cytochrome c represses ferroptosis Song et al. demonstrated that the cytosolic CYCS-INPP4A complex inhibits ferroptosis by promoting phosphatidylinositol-3-phosphate synthesis and preventing phospholipid peroxidation. The small molecule 10A3 disrupts this complex, enhancing ferroptosis-mediated tumor suppression and offering a therapeutic strategy.

Online now: Cytosolic cytochrome c represses ferroptosis

Leveraging genetics to understand ADAR1-mediated RNA editing in health and disease Nature Reviews Genetics, Published online: 14 April 2025; doi:10.1038/s41576-025-00830-5ADAR1-mediating RNA editing enables the cell to distinguish between endogenous and viral RNA. Li and Walkley review findings from human and mouse genetics that have revealed the mechanisms of ADAR1-mediated RNA editing, which are now providing insights for the development of potential therapies that target these mechanisms.

New online! Leveraging genetics to understand ADAR1-mediated RNA editing in health and disease

MLKL activity requires a splicing-regulated, druggable intramolecular interaction Necroptosis is an inflammatory form of regulated cell death implicated in a range of human pathologies, whose execution depends on the poorly understo…

‘MLKL activity requires a splicing-regulated, druggable intramolecular interaction’

www.sciencedirect.com/science/arti...

NEWS: NICE has recommended capivasertib for advanced #BreastCancer.

The decision makes the targeted drug available, in combination with fulvestrant, for some NHS patients with the most common type of breast cancer.

Read more about the history of the drug⬇️
www.icr.ac.uk/about-us/icr...

BREAKING NEWS: #ProstateCancer spit test is better for men with high genetic risk than the standard PSA blood test.

The results from the ICR's BARCODE 1 trial are published in @nejm.org

More here ⬇️
icr.ac.uk/about-us/icr-news/detail/simple-spit-test-could-finally-turn-the-tide-on-prostate-cancer

Assessment of a Polygenic Risk Score in Screening for Prostate Cancer | NEJM The incidence of prostate cancer is increasing. Screening with an assay of prostate-specific antigen (PSA) has a high rate for false positive results. Genomewide association studies have identified...

impactful work from @icr.ac.uk - saliva test to identify men at risk of prostate cancer www.nejm.org/doi/full/10....

News write up here : www.bbc.co.uk/news/article...

Neoantigen-specific tumor-infiltrating lymphocytes in gastrointestinal cancers: a phase 2 trial - Nature Medicine In an iterative phase 2 trial, patients with metastatic, treatment-refractory, mismatch repair proficient gastrointestinal cancers had responses to neoantigen-reactive tumor-infiltrating lymphocytes b...

Neoantigen-specific tumor-infiltrating lymphocytes in gastrointestinal cancers: a phase 2 trial

www.nature.com/articles/s41...

Skin damage signals mediate allergic sensitization to spatially unlinked antigen Skin injury releases damage-encoded systemic signals that can initiate immunity to novel antigens introduced at distal barrier sites.

‘Skin damage signals mediate allergic sensitization to spatially unlinked antigen’

www.science.org/doi/10.1126/...

Mitochondrial respiratory complex IV deficiency recapitulates amyotrophic lateral sclerosis - Nature Neuroscience Cheng et al. identify a mitochondrial complex IV (CIV) deficiency in the brains of patients with sporadic amyotrophic lateral sclerosis (ALS). They demonstrate that defects in mitochondrial CIV induce...

Whoa - are a significant proportion of sporadic ALS/motor neuron disease cases a mitochondrial DNA disease?! #mitochondria
www.nature.com/articles/s41...

TBK1 and IKKε prevent premature cell death by limiting the activity of both RIPK1 and NLRP3 death pathways TBK1 and IKKe prevent premature cell death by limiting the activity of multiple death pathways in myeloid cells.

The loss of TBK1, or both TBK1 and the related kinase IKKε, results in uncontrolled cell death–driven inflammation. We show that TBK1/IKKε prevent premature cell death by limiting the activity of multiple death pathways in myeloid cells. www.science.org/doi/10.1126/...