Study finds obese patients respond better to treatment.

Obesity is one of the top risk factors for cancer – along with smoking. But obese cancer patients often respond better to immunotherapy than others. Researchers at the University of California Davis (UC Davis) might have found a reason for this.  

Overweight people have weakened immune systems and tend to produce more of the compounds that encourage tumor growth – particularly the PD-1 protein on the surfaces of T cells. These same molecules are the key targets of cancer immunotherapies known as checkpoint inhibitors – making them more effective for many obese patients.

In fact, checkpoint inhibitor therapy can be quite effective, making many different types of tumors disappear for years – but it only works for a limited number of patients, with a disproportionate number of them being overweight.

The UC Davis researchers found that the T cells of obese mice, monkeys, and people were “exhausted” – slow to proliferate and no longer producing proteins that stimulate other immune system compounds – and had more PD-1 protein than average. The excess PD-1 is in part due to greater amounts of leptin, which is present in fat cells. The researchers believe that the leptin triggers a signaling pathway that increases PD-1 on T cells.

Other researchers are now exploring the possibility of incorporating a high-fat diet with checkpoint inhibitor therapy to see if results improve. Such a diet can have negative health consequences overall, however, so a balance must be maintained.