Why young and female patients don't respond as well to cance
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Cancer immunotherapy—empowering a patient's own immune system to clear away tumors on its own—holds great promise for some patients. But for other patients, immunotherapy just doesn't work.

Their findings suggest that since the typically robust immune systems of young and female patients are better at getting rid of tumor cells, the cells left behind are not as readily visible to the immune system to begin with, rendering some types of immunotherapy ineffective.

Sex and age differences have long been observed when it comes to immune response. For example, females have twice the antibody response to flu vaccines and are far more susceptible to autoimmune diseases. Similarly, human immune systems tend to weaken as we age. But if females and younger people have stronger immune responses in most cases, you might expect cancer immunotherapy to work better for them, not worse.

The Team looked at genomic information for nearly 10,000 patients with cancer available from the NIH's The Cancer Genome Atlas, and another 342 patients with other tumor types.

What they did find was that, compared to older and male patients with cancer, younger and female patients tend to accumulate more cancer-causing genetic mutations of the sort that MHCs can't present to the immune system as efficiently.

Authors said this is likely because robust immune systems of the young and female are better at getting rid of cells displaying well-presented mutant self-antigens, leaving behind tumor cells that rely more heavily on the poorly presented mutations. This selective pressure is known as immuno-editing.

"So if a tumor cell doesn't present highly visible, mutated self antigens to begin with, checkpoint inhibitor drugs can't help reveal them to the immune system," they said.

The more we learn about how interactions between tumors and immune systems might vary, the better positioned we are to tailor treatments to each person's situation.

Source: https://www.nature.com/articles/s41467-020-17981-0
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