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Immunology Update - July 2019

Welcome to the next installment of our regular update where we report on research from the world of immunology, highlighting work from BSI members that has hit the headlines over the past few weeks.


Selecting the best T cell for the job

A new study by researchers at Cardiff University has revealed that increasing the amount of a molecule called L-selectin on T cells increases their ability to fight solid cancer tumours. Current altered T cell immunotherapies have mostly been used to treat leukaemia, where cancer cells are circulating in the blood and therefore easily accessible. Solid tumours have poor blood flow and their blood vessels are not properly formed, so they are more difficult to treat with this type of therapy currently.

In mouse models, the new research published in Frontiers in Immunology showed very promising results for improving control of tumour growth. L-selectin T cells were able to work in synergy with current checkpoint blockade inhibitor therapies to halt tumour growth. The authors are hopeful that, by editing T cells to maintain L-selectin expression, they will be able to broaden the clinical scope of CAR-T therapies.

L-selectin is a T cell activation marker and homing molecule. Surprisingly, extra L-selectin did not improve T cell homing. The benefit likely comes from activation and retention of anti-cancer T cells inside the tumour. BSI Trustee Professor Ann Ager from Cardiff University, who led the study, said, “The modified T-cells entered solid cancers within the first hour and kept accumulating inside the solid cancers over more than a week, suggesting that L-selectin also plays a role in activation and retention of anti-cancer T cells inside cancers.”

While more study is needed before this can enter the clinic, it is a promising step toward an engineered T cell immunotherapy for solid tumours.

Read the press release here

Read the full article here: Watson et al. 2019 Frontiers in Immunology. DOI: https://doi.org/10.3389/fimmu.2019.01321


The genes behind your cavities

New research from an international collaboration led by the University of Bristol suggests hereditary traits affecting cardiovascular health also affect the health of our mouths. An analysis of nine international clinical studies has found 47 new genes with connections to tooth decay and confirmed previously suggested links.

It has been known for many years that gum disease is linked to cardiovascular disease through increased inflammation as the immune system reacts to unhealthy bacteria in the mouth. Published in Nature Communications, this study suggests the link goes deeper, to the gene level. Researchers think that heritability of tooth decay may be shared with a range of complex traits that are cardiometabolic risk factors, such as smoking and obesity.

Author Professor Ingegerd Johansson of Umeå University, Sweden said, "The study makes it clear that teeth are part of the body.  Among other things, we can see that there seems to be a causal link between risk factors for cardiovascular disease and tooth decay."

Risk loci included the HLA region that is associated with immune receptors and WNT10A, which is linked to regulating tooth formation. The new evidence suggests that processes linked to tooth decay may have negative effects on health in later life. One example is that dental diseases resulting in dentures were found to be a risk factor for cardiovascular disease. The authors hope that by improving genetic understanding they will be able to improve risk assessment and outcome prediction.

Read the press release here

Read the full paper here: Shungin et al. 2019 Nature Communications DOI: https://doi.org/10.1038/s41467-019-10630-1


Having the guts to fight the flu

New research from the Francis Crick Institute, published in Cell Reports, has discovered that gut bacteria may be important in lung defence.

Researchers found that microbiota-driven interferon signals from the gut were able to keep antiviral genes in lung cells active. This allowed the cells lining the lung to keep the virus under control until the immune system could respond. Without the signals from the gut, the virus was able to replicate to much higher levels, requiring a stronger and more damaging immune response. In mice, those with healthy gut bacteria survived the flu 80% of the time, whereas mice treated with antibiotics only survived 30% of the time.

Dr Andreas Wack, who led the research, said, “We found that antibiotics can wipe out early flu resistance, adding further evidence that they should not be taken or prescribed lightly. Inappropriate use not only promotes antibiotic resistance and kills helpful gut bacteria, but may also leave us more vulnerable to viruses."

To confirm the protection was originating from the gut rather than the lung, researchers treated mice with antibiotics, then repopulated their gut bacteria through a faecal transplant. The transplant restored interferon signalling and flu resistance, suggesting gut bacteria have a crucial role in immune defences. This could also be relevant to livestock animals, who commonly receive prophylactic antibiotic treatments. Further research is needed to determine if this makes them more susceptible to viral infections.

Read the press release here

Read the full paper here: Bradley et al. 2019 Cell Reports DOI: https://doi.org/10.1016/j.celrep.2019.05.105