Non-Small Cell Lung Cancer Coverage from Every Angle

Can Supertype B44 HLA Antigen Shape Tumor Response in NSCLC?

By: Noelle Cutter, PhD
Posted: Wednesday, February 17, 2021

Researchers at UCLA Jonsson Comprehensive Cancer Center explored the role of the B44 supertype HLA antigen in response to immune checkpoint inhibitors in cancer treatment. In Nature Cancer, Edward B. Garon, MD, of David Geffen School of Medicine, and colleagues reported that although this specific HLA antigen may be associated with improved survival in patients with melanoma treated with these immunotherapeutic agents, this effect was not seen in patients treated with immune checkpoint inhibitors for non–small cell lung cancer (NSCLC). The investigators believe their study findings may improve the assessment of HLA-related outcomes and predict the benefit from such immunotherapy in those who have B44. 

“From the time that we discovered the contradictory outcomes in HLA-B44 patients with melanoma and non–small cell lung cancer, we became fascinated by the mechanism that could explain this,” revealed Dr. Garon in a UCLA press release. “This certainly has a lot of implications for how we run clinical trials and may be able to help us stratify patients much better in terms of their likelihood of response to immunotherapy,” commented coauthor Amy L. Cummings, MD, also of Jonsson Cancer Center.

The authors used whole-genome sequencing to reevaluate immune checkpoint inhibitor–associated survival in NSCLC and melanoma based on the presence of HLA genotypes. They focused mainly on 65 tissue samples from patients with NSCLC treated with single-agent pembrolizumab; in addition, they validated their findings with publicly available NSCLC and melanoma cohorts. The researchers determined specific amino acid mutations that substitute glycine for glutamic acid at anchor positions through this analysis. This mutation allows for enhanced peptide-MHC binding and seemed to correlate with better survival in melanoma, but not NSCLC. 

The researchers believe their data may help clinicians to predict patient response to immune checkpoint inhibitors, depending on favorable or unfavorable B44 neoepitopes. Therefore, these peptides may be used as a prognostic marker for patient stratification in melanoma and NSCLC.

Disclosure: The study authors reported no conflicts of interest.

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