Inhibitory T cell checkpoint molecules sit on the surface of cancer cells, where they inhibit the surrounding immune response and thus secure the survival and proliferation of underlying cancer cells. Immune checkpoint blockade (ICB) treatments block these molecules, and thus ‘take off the immune system’s brakes’ so it can destroy these cells.
So far, ICB therapy has revolutionized cancer treatments: the five-year survival rate for advanced melanoma- the most advanced kind of skin cancer- has risen from under 10% to 50% since its introduction in 2011. Why 50% of patients do not respond to the treatment, however, has remained unknown. In the current study, researchers set out to find out why this may be the case.
To do so, they analyzed healthcare data from the Cancer Genome Atlas, a public database with information on 20,000 tumors from 33 cancer types. In doing so, they discovered that patients with certain types of skin, lung, bone and soft tissue, breast, and cervical cancers and higher levels of CD5+ dendritic cells in their tumors responded better to ICB therapy. CD5+ dendritic cells are important for immune T cell receptor signaling and thus, the immune response.
The researchers next tested their findings on human and mouse cells. They found that CD5+ dendritic cells from people induced T cells to activate and multiply. They also found that mice with tumors responded weakly to immunotherapy and failed to reject tumors if they lacked CD5 on their dendritic cells. The researchers further found that immune protein IL-6 increases numbers of CD5+ dendritic cells.
They concluded that their findings mean that the number of CD5+ dendritic cells inside tumors could help doctors assess which patients are most likely to benefit from immunotherapy. They also noted that increasing the number or activity of the cells could help more people benefit from immunotherapy.
“We still don’t completely understand how immunotherapies work,” said senior author Eynav Klechevsky, Ph.D., an assistant professor of pathology & immunology, in a press release.
“This study indicates that there is more we can do to increase the efficacy of these treatments. I’m confident that if we can find ways to harness these cells or expand these cells in patients, we can help more people,” she added.
Sources: EurekAlert, Science