Patient-specific HLA-I subtypes predict response to immune checkpoint blockade

Area of Science:

• Immunogenetics
• Oncology
• Clinical Immunology

Background:

• Immune checkpoint blockade (ICB) therapy has revolutionized cancer treatment.
• Identifying predictive biomarkers for ICB response is crucial for optimizing patient outcomes.
• Human Leukocyte Antigen (HLA) class I alleles have been implicated in immune responses, including those to ICB.

Purpose of the Study:

• To identify specific HLA-A subtypes associated with maximal clinical benefit from ICB therapy.
• To investigate the relationship between HLA-A subtypes and ICB efficacy in patients with solid cancers.

Main Methods:

• A clinical dataset of 285 patients undergoing germline HLA status testing was compiled.
• HLA-A genotyping was performed to identify specific subtypes.
• Patient response status to ICB was evaluated.

Main Results:

• Fifteen HLA-A subtypes were identified, with HLA-A02, HLA-A01, and HLA-A03 being the most common.
• The HLA-A02:01 subtype exhibited a tumor lineage-specific distribution.
• Patients with the HLA-A01 subtype demonstrated significantly better clinical outcomes following ICB.
• No significant association was found between HLA-A subtypes and immune-related adverse effects.

Conclusions:

• Specific HLA-A subtypes, notably HLA-A01, are associated with improved response to ICB in solid cancer patients.
• HLA genotyping can serve as a predictive and selective biomarker for ICB therapy.
• Early integration of HLA genotyping into the diagnostic work-up for solid cancer patients receiving ICB is recommended.