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How cancer stem cells dodge the immune system


Cancer stem cells are tricky beasts. They are often resistant to common treatments and can hide out in the body long after the bulk of tumor cells have been eliminated. Over time, they're thought to contribute to the recurrence of disease in seemingly successfully treated people.

Stanford head and neck surgeon John Sunwoo, MD, and graduate student Yunqin Lee have been investigating how stem cells in head and neck cancers manage to evade the body's immune system. Although it's been known that a type of head and neck cancer cells -- CD44+ cells -- are particularly resilient to treatment, it's not been known exactly how they accomplish this feat.

Now, Sunwoo and Lee published today in Clinical Cancer Research a study that sheds some light on the issue. They found that a protein called PD-L1 is expressed at higher levels on the surface membrane of CD44+ cells than on other cancer cells. PD-L1  is believed to play a role in suppressing the immune system during pregnancy and in diseases like hepatitis. It does so by binding to a protein called PD-1 on a subset of immune cells (T cells) and dampening their response to signals calling for growth and activation.

As Sunwoo described to me in an email:

We believe that our work provides very important insight into how cancer stem cells, in general, contribute to tumor cell dormancy and minimally residual disease that may recur years later. Our findings also provide rationale for targeting the PD-1 pathway in the adjuvant therapy setting of head and neck cancer following surgical resection.

Importantly, researchers and clinicians have previously found that treating patients with antibodies to block this pathway in metastatic melanoma, non-small-cell lung cancer and kidney cancer can lead to durable regression or stabilization of disease. The new findings presented by Sunwoo's group help explain these long-lasting beneficial effects, and also indicate that this pathway is an important target in head and neck cancer. Furthermore, Sunwoo and his colleagues also showed that PD-L1 expression on the CD44+ cells initiates a series of signaling events within the cells that could reveal valuable targets when designing future therapies.

As Sunwoo described:

Given the revolutionary use of antibodies to block the interaction between PD-L1 on cancer cells with PD-1 on T cells, and how this strategy has not only validated the immunotherapy approach for cancer within the last two years but has also transformed how we approach metastatic disease in multiple solid malignancies, we believe this is an important mechanism by which cancer stem cells evade the host immune system.

Previously: Common drug class targets breast cancer stem cells, may benefit more patients, says studyWeakness in lung cancer stem cells identified by Stanford scientists  and Stanford surgeon uses robot to increase precision, reduce complications of head and neck procedures 
Photo by Jaron

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