A new study published in Nature Communications by experts at the UC Davis Comprehensive Cancer Centre reveals an unexpected evolutionary twist: a minor genetic alteration in humans may make our immune system less efficient against certain solid tumours than that of our monkey ancestors. This research could lead to better cancer treatments in the future. 

Researchers discovered a small change in a protein known as Fas Ligand (FasL). FasL is present on the surface of immune cells. It operates as a "kill switch", inducing apoptosis, or programmed cell death, to remove cancer cells. When immune cells, such as CAR-T cells (engineered T cells derived from a patient's immune system), attack cancer, they rely on FasL to eradicate the tumour. 

However, the study discovered that in humans, a single mutation in the FasL gene renders this death switch vulnerable. Humans have serine at position 153 of FasL, but chimps and other animals have proline there. This minor variation implies that in humans, the protein is easily cleaved and deactivated by an enzyme known as plasmin. 

Plasmin is a protease, an enzyme that degrades proteins. It is frequently discovered in high concentrations in aggressive solid tumours, such as triple negative breast cancer, colon cancer, and ovarian cancer. When plasmin cuts FasL, it essentially disables the immune cell's ability to attack cancer cells. 

"The evolutionary mutation in FasL may have contributed to humans' greater brain sizes. "However, in the case of cancer, it was an unfavourable tradeoff because the mutation allows specific tumours to disarm sections of our immune system," Dr. Jogender Tushir-Singh, the senior author of the study, stated. 

This discovery could potentially resolve a challenging issue in cancer treatment. CAR-T treatments have demonstrated great success in treating blood cancers such as leukaemia, but they frequently fail in solid tumours. Blood malignancies rarely need plasmin to spread, although solid tumours usually do. The tumour environment effectively neutralises the immune system's primary weapons. 

Importantly, the study identified a potential solution. In lab tests, researchers discovered that stopping plasmin or changing FasL so it doesn't get cut helped immune cells fight cancer cells better. This evidence shows that combining plasmin inhibitors with existing immunotherapies could significantly increase their efficacy against solid tumours. 

"Humans have a far higher cancer rate than chimps and other monkeys. 'There is a lot that we don't know and can still learn from primates to improve human cancer immunotherapies,' Dr Tushir-Singh stated." 

In short, our evolutionary route may have resulted in evolved brains, but it may also have made us more susceptible to cancer. But this awareness provides hope. Understanding the involvement of plasmin and the vulnerability of FasL may allow scientists to build novel medicines that boost our immune system's attack on solid tumours.