PD-L1 Expression Associated With Radiation Resistance in Head and Neck Cancer

Submitted by admin5 on Tue, 05/16/2017 - 17:20

PD-L1 expression may be a biomarker of local failure in human papillomavirus (HPV)-negative head and neck squamous cell carcinoma following radiotherapy, according to research published in Clinical Cancer Research (published online May 2017; doi:10.1158/1078-0432.CCR-16-2586).

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Treatment advances in recent years have contributed to improved outcomes in HPV-negative head and neck cancer. However, locoregional failure resulting from failed radiotherapy occurs in up to 50% of cases and is the primary contributor to death in patients with the disease. There has yet to be any biomarkers of response discovered for HPV-negative head and neck cancer.

Heath D Skinner, MD, PhD, MD Anderson Cancer Center (Houston, TX), and colleagues conducted a study to examine cell lines and tumor specimens in HPV-negative disease. Researchers utilized cell lines with acquired resistance to radiation, a panel of HPV-negative disease cell lines, and tumor specimens from 3 cohorts of patients with HPV-negative disease (n = 68, 97, and 114).

Researchers found that radiation resistant cell lines exhibited upregulation of the proteins Axl, markers of PI3K/AKT/mTOR pathway activation, and PD-L1 in the cells with acquired resistance to radiation. Inhibition of either AxI or PI3 kinase led to decreased PD-L1 expression.

After multiple tests, PD-L1 was confirmed to correlate with both AxI and PI3 signaling as well as with local failure following radiotherapy. This finding was validated using a third cohort, in which researchers found that tumors exhibiting high expression of PD-L1 had local failure rates following radiotherapy of 60%, 70%, and 50% compared with 20%, 25%, and 20% in the PD-L1–low expression group (P = 0.01, 1.9 × 10−3, and 9 × 10−4, respectively).

“These findings provide a strong rationale for the combination of immune checkpoint blockade and radiation in this setting, as well as potentially utilizing Axl or PI3 kinase blockade to affect both tumor radiosensitization and immune response," said the authors in a press release (May 9, 2017).

The authors also acknowledged that a significant association exists among CD8 infiltrate, PD-L1, and response to radiation, though patients who had CD8-positive TILs but were PD-L1 negative experienced no local failures and no disease-related deaths. — Zachary Bessette