Medical Bulletin 16/September/2022

A new mechanism that slows down and may even prevent the natural ageing of immune cells – one of the nine 'hallmarks of ageing'* – has been identified by an international team led by UCL scientists. Published in Nature Cell Biology, researchers say the discovery in-vitro (cells) and validated in mice was 'unexpected' and believe harnessing the mechanism could extend the life of the immune system, allowing people to live healthier and longer, and would also have clinical utility for diseases such as cancer and dementia.

With the immune system no longer functioning effectively, this leads to the onset of chronic infections, cancerous disease and death. Telomere attrition has been described as one of the 'hallmarks of ageing'*.

Reference:

Dr Alessio Lanna et al,Intercellular telomere transfer rescues T cells from senescence and promotes long-term immunological memory, Nature Cell Biology, DOI: 10.1038/s41556-022- 00991-z

Drugs like enzalutamide that inhibit male hormones from activating the androgen receptor have been used to treat advanced prostate cancer for more than a decade. A new study from the University of Michigan Rogel Cancer Center suggests androgen receptor inhibitors can fundamentally rewire and reshape how prostate tumors function, and in certain cases even make them more aggressive. These findings have been published in Nature Communications.

Male hormones function as fuel, turning on the androgen receptor that acts as the engine of prostate cancer cells. The researchers wanted to understand what was present in these tumors, to begin with and what happened after tumors started to grow on enzalutamide treatment. They recruited patients to a longitudinal study to obtain metastatic biopsies before enzalutamide treatment and at the time the tumor became resistant to treatment. His team collected serial biopsies from 21 patients, enabling them to understand the workarounds in the tumor from each patient.

Reference:

Joshi Alumkal et al,Transcriptional profiling of matched patient biopsies clarifies molecular determinants of enzalutamide-induced lineage plasticity,Nature Communications,DOI 10.1038/s41467-022-32701-6

A single research test has the potential to predict which patients treated with immunotherapies-which harness the immune system to attack cancer cells-are likely to have their cancer recur or have severe side effects, a new study found. Published online in Clinical Cancer Research, the study revolved around the set of immune system signaling proteins called antibodies that recognize invading bacteria, viruses, and fungi. These blood proteins are designed to glom onto and inactivate specific bacterial and viral proteins, but in some cases "autoantibodies" also react to the body's "self" proteins to cause autoimmune disease.

The researchers obtained blood samples from more than 950 patients enrolled in one of two Phase 3 randomized controlled trials of adjuvant checkpoint inhibitors in patients with advanced melanoma. Tumors in these patients had been surgically removed and blood samples collected before they received any treatment. The new test employs a microchip with 20,000 proteins attached in specific spots. When an antibody recognizes any of the proteins present in a blood sample, those spots glow with the signal intensifying as the concentration of antibody increases.

Reference:

Paul Johannet et al,Baseline serum autoantibody signatures predict recurrence and toxicity in melanoma patients receiving adjuvant immune checkpoint blockade,Clinical Cancer Research