Publication highlights

Researchers from the Francis Crick Institute, UCL, Gustave Roussy and Memorial Sloan Kettering Cancer Center (MSK), have discovered that expansion of mutant blood cells, a phenomenon linked to ageing, can be found in cancerous tumours, and this is associated with worse outcomes for patients. Clonal haematopoiesis of indeterminate potential (CHIP) is a condition where blood stem cells accumulate mutations over time. The researchers found that tumour-infiltrating clonal haematopoiesis, not CHIP alone, was associated with greater risk of relapse and cancer death. Patients with TI-CH had an expansion of myeloid cells which can support tumour progression and support. They also discovered that blood cells with TET2 mutations were more likely to be tumour-infiltrating, and that TET2 mutant myeloid cells remodelled the tumour microenvironment. Finally, they validated their findings in over 49,000 patients, finding that mutations were more common in harder-to-treat cancer types.

To mount a robust immune response, immune cells called IgG1 B cells must be selected within the germinal centres of lymphoid organs to produce high affinity antibodies against pathogens. Despite the importance of this process, its mechanism remains largely elusive. By investigating the role of genes in germinal centre B cells, researchers at the Crick revealed that a protein called MIZ1 was critical for the selection of IgG1 B cells and production of high-affinity antibodies. Specifically, MIZ1, a protein known for its role in gene regulation, was identified as a key player in driving the expression of TMBIM4, which ultimately prevented IgG1 B cell death due to excessive calcium signalling, ensuring IgG1 B cell survival during the critical selection process. These findings underscore the significance of MIZ1 and TMBIM4 in shaping the immune response during infection and vaccination.

Researchers in the Kassiotis lab have shown that a specific area of the SARS-CoV-2 spike protein is a promising target for a pan-coronavirus vaccine that could offer some protection against new virus variants, common colds, and help prepare for future pandemics.

Researchers in the Reis e Sousa lab have found how the immune system triggers an ‘emergency’ dendritic cell response during infection. Dendritic cells have an important role in the immune system, detecting infectious bacteria, fungi or viruses that have entered the body and alerting T cells which recognise and attack the invader. However, there are few dendritic cells in healthy tissue like the lungs which means that, on infection, their numbers need to be boosted. In their study, the team monitored dendritic cells in mice infected with flu virus and found that, after infection, new dendritic cells are released from the bone marrow in response to a chemokine ‘distress’ signal which directs them to the site of infection.

Using advanced bioinformatics approaches, we deciphered the global transcriptional response in the lungs of mice infected or challenged with a broad spectrum of infectious pathogens, including parasites, bacteria, viruses, fungi, or allergens; we also determined to what extent each of these responses is preserved in the blood. We demonstrated a unique global transcriptional signature for each of the different diseases in both lung and blood. The lung transcriptional signatures showed a gradation, ranging from IFN-inducible gene clusters, to those associated with granulocyte/neutrophil/IL-17 dominated genes, to responses dominated by expression of genes encoding TH2 cytokines, mast cells and B cells.