PD-L2 Expression and Clinical Response to Pembrolizumab in Head and Neck Cancer

Key Points

  • PD-L2 expression was observed in the seven tumor types examined, including renal cell carcinoma, bladder, melanoma, non–small cell lung cancer, triple-negative breast cancer, gastric carcinoma, and head and neck squamous cell carcinoma, and was expressed in the absence of PD-L1 in subsets of patient samples.
  • PD-L2 expression was independently associated with clinical response in patients with head and neck squamous cell carcinoma treated with pembrolizumab, indicating that the presence or absence of PD-L2 expression may also play a role in response to PD-1 axis–targeted therapies.
  • Therapy targeting both PD-1 ligands may provide clinical benefit in patients with head and neck squamous cell carcinoma.

A study assessing the prevalence and distribution of programmed cell death ligand 2 (PD-L2) in human tumor samples across seven cancer indications, including renal cell carcinoma, bladder, melanoma, non–small cell lung cancer, triple-negative breast cancer, gastric carcinoma, and head and neck squamous cell carcinoma, has found PD-L2 expression in all the tumor types, and it was expressed in the absence of PD-L1 in subsets of the patient samples. In addition, PD-L2 expression was independently associated with improved clinical outcomes in pembrolizumab (Keytruda)-treated patients with head and neck squamous cell carcinoma and may be partly related to blockade of PD-L1/PD-L2 interactions. The findings suggest that targeting both PD-L1 ligands may provide clinical benefit in these patients. The study by Yearley et al was published in Clinical Cancer Research.

Study Details and Results

The researchers developed a novel immunohistochemical (IHC) assay to assess PD-L2 expression in over 400 archival tumor samples across the 7 cancer types. In addition, relationships between clinical response and PD-L2 status were evaluated in tumor tissues from patients with head and neck squamous cell carcinoma with recurrent or metastatic disease treated with pembrolizumab.

PD-L2 expression was observed in all tumor types and was present in stromal, tumor, and endothelial cells. The prevalence and distribution of PD-L2 correlated significantly with PD-L1 (P = .0012 to < .0001); however, PD-L2 was detected in the absence of PD-L1 in some tumor types. Both PD-L1 and PD-L2 positivity significantly predicted clinical response to pembrolizumab on combined tumor, stromal, and immune cells, with PD-L2 predictive independent of PD-L1. Response was greater in patients who tested positive for both PD-L1 and PD-L2 (27.5%) than in those who tested positive only for PD-L1 (11.4%). PD-L2 status was also a significant predictor of progression-free survival, with pembrolizumab independent of PD-L1 status. Longer median times for progression-free and overall survival were observed for PD-L2–positive than PD-L2–negative patients.

Clinical Implications

“We are all aware that PD-L1 is a marker with varying degrees of predictive ability in different tumor types,” said Jennifer H. Yearley, DVM, PhD, Senior Principal Scientist of Anatomic Pathology at Merck Research Laboratories and lead author of this study, in a statement. “There are individuals who are PD-L1–positive who don’t respond and people who are PD-L1–negative who do respond.”

“This [study] suggests that PD-L2 expression may provide information beyond that of PD-L1 in predicting clinical response to anti–[programmed cell death protein 1]–targeted agents, which block the interactions of both PD-L1 and PD-L2 with PD-1 and may help in identifying patients who may derive benefit from these therapies. Further studies are needed to more fully understand the clinical relevance and predictive value of PD-L2 in cancer immunotherapy,” concluded the study authors.

This study was funded by Merck & Co.

 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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