PD-L2 Expression May Indicate Response to Immunotherapy in Head and Neck Cancer

A recent study suggests that immunotherapies targeting both PD-L1 and PD-L2 may enhance response rates for patients with head and neck squamous cell carcinoma (HNSCC), published in Clinical Cancer Research (published online June 2017; doi:10.1158/1078-0432.CCR-16-1761).


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"It is well known that PD-1 has two binding partners, PD-L1 and PD-L2, yet most of the published work to date has looked at the distribution and predictive benefits of PD-L1 expression alone," said Jennifer H Yearley, DMV, PhD, senior principal scientist of Anatomic Pathology, Merck Research Laboratories (Palo Alto, CA), in a press release (June 15, 2017).

Yearly and colleagues conducted a study aimed to determine the association between PD-L2 expression and its relationship with response to pembrolizumab for patients with HNSCC.

Using the novel immunohistochemistry assay, researchers examined more than 400 archival tumor samples across the following 7 types of cancer: renal cell carcinoma, bladder, melanoma, non-small cell lung cancer, triple negative breast cancer, gastric carcinoma, and HNSCC. They found that PD-L2 was commonly expressed across all of the tumor types, most prominently in HNSCC. PD-L2 expression was observed in more than half of the HNSCC samples.

Researchers next evaluated tumor samples from 172 patients with recurrent or metastatic HNSCC. Participants in this trial comprised two combined cohorts that had been assigned pembrolizumab treatment. Researchers discovered that patient response was significantly associated with PD-L2 expression, which indicated that therapy targeting both PD-L1 and PD-L2 may improve patient response rates.

"The overall response rate (ORR) for the two KEYNOTE-012 cohorts in this study was 27.5 percent among patients whose tumors were positive for both PD-L1 and PD-L2, more than two times higher than the 11.4 percent ORR for patients whose tumors were positive only for PD-L1," Yearley said. “The researchers also found that PD-L2 positivity was associated with longer overall survival (OS), and median OS times were 303 days and 109 days respectively.”

Overall, the study indicated that PD-L2 expression may provide additional information beyond PD-L1 positivity in predicting clinical response to anti-PD-1 therapies in HNSCC patients. This finding may have prognostic implications for patients with HNSCC.—Christina Vogt