Figure 2.

Antigen Presentation Genomic Diversity and Expression Is Associated with Response to Immune Checkpoint Blockade

(A) There were no differences in the number of germline HLA class I alleles or the degree in homozygosity found between responders and non-responders. HLA class I germline zygosity and somatic HLA class I LOH were combined to calculate the unique number of HLA class I alleles in tumor cells. The β₂-microglobulin locus frequently underwent monoallelic loss, but there was no evidence pointing to an enrichment in concurrent inactivating mutations in tumors from non-responder patients. HLA class I and II as well as β₂-microglobulin expression was significantly higher in tumors from responding patients.

(B) HLA class II genotypes for DPA1, DPB1, DQA1, DQB1, and DRB1 were derived from whole-exome sequence data. Patients with maximal heterozygosity for HLA class II (HLA class II alleles = 10) had a significantly longer progression-free survival (log rank p = 0.043).

(C and D) Patients heterozygous at the HLA-PD locus and more specifically at the HLA-DPB1 locus had a significantly longer progression-free survival (log rank p = 0.007 and p = 0.005, respectively).