Hiding in Plain Sight

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Study examines a drug that can boost the immune system’s ability to detect cancer.
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One way that cancer escapes immune detection is by gaining features that make tumour cells indistinguishable from normal cells, such that no threat is detected.

Surveillance cameras and security systems are often used to protect against criminal activity. Their effectiveness, however, depends on their ability to identify suspicious activity.

Just as some criminals can avoid detection by obscuring themselves from surveillance cameras, cancer cells in the body have features that enable them to evade the body’s immune system.

To this end, researchers are developing new strategies—collectively known as immunotherapy—to boost the immune system’s ability to detect and eliminate tumours.

Among the many types of immunotherapy is a class of drugs known as checkpoint inhibitors, which ‘release the brakes’ on the immune system and unleash powerful immune cells that migrate to and destroy tumours. The checkpoint inhibitor, ipilimumab, is an effective drug for several types of cancer, but its usefulness in treating women with cervical cancer—over 90% of whom have an associated infection with human papillomavirus (HPV)—is not known.

Dr. Amit Oza (PM Clinical Researcher and Director of the Bras Family Drug Development Program) initiated a clinical trial to address this gap in knowledge. A part of the Princess Margaret Phase II Consortium, the trial followed 42 women with HPV-related cervical cancer who were treated with ipilimumab. The drug was generally considered safe, although some unwanted effects were seen in certain patients.

The research team found that few immune cells were present in patients’ tumour tissues, suggesting that immune cells were not migrating to the tumour. Furthermore, the treatment did not stop the progression of cancer in the majority of patients. The team also found that immune cells circulating in the blood were primed for action, despite the lack of anti-tumour activity.

“Our study is the first to evaluate the effectiveness of ipilimumab in HPV-associated cervical cancer,” says Dr. Oza. “While the drug did not demonstrate significant anti-tumour activity on its own, it is clearly activating immune cells in the blood. As such, its effectiveness combined with other drugs—for example those that target cancer’s ability to evade the immune system—warrants further investigation.”

This work was supported by the National Institutes of Health and The Princess Margaret Cancer Foundation.

Lheureux S, Butler MO, Clarke B, Cristea MC, Martin LP, Tonkin K, Fleming GF, Tinker AV, Hirte HW, Tsoref D, Mackay H, Dhani NC, Ghatage P, Weberpals J, Welch S, Pham NA, Motta V, Sotov V, Wang L, Karakasis K, Udagani S, Kamel-Reid S, Streicher HZ, Shaw P, Oza AM. Association of ipilimumab with safety and antitumor activity in women with metastatic or recurrent human papillomavirus-related cervical carcinoma. JAMA Oncol. 2017 Nov 16. doi: 10.1001/jamaoncol.2017.3776.