MA11.11 Discrepancy of Tumor Neoantigen Burden Between Primary Lesions and Matched Metastases in Lung Cancer

Abstract

Personalized vaccine based on tumor neoantigens showed the striking antitumor effect on several solid tumors, suggesting its significant and potential role in curing cancer. However, whether tumor neoantigens identified from primary lesions were similar to their matched metastases remain unknown. Here, we aimed to compare the tumor neoantigen burden (TNB) between primary lesions and matched metastases in lung cancer. Primary lung cancers, matched metastatic sites and peripheral blood (10 mL, EDTA) were collected before any systemic therapy as part of the standard clinical care. Genomic DNA was extracted from all included samples. The matched peripheral blood leukocytes were used as the source for germline DNA control. DNA libraries were subjected to whole-exome capture and then sequenced on an Illumina HiSeq X-TEN platform. The criteria for tumor neoantigen identification were tumor specific mutations (missense, frameshift, inframe insertion or deletions), fold change > 10, high predicted affinity (IC50 < 500 nM) and predicted peptide of 9-10 amino acids in length. Totally, 14 cases with matched lung primary lesions and metastases were enrolled, including 10 patients with liver metastases and 4 with brain metastases. A wide range of TNB were identified in both primary lesions (median 157, range 21-1156) and metastases (median 135, range 35-1902). We observed a large discrepancy of TNB between primary lesions and matched metastases, with a median unique percentage of 82.20% (74.03%-95.24%) in primary lesions and 84.50% (77.45%-97.14%) in metastases. In patients with brain metastases, primary lesions had a percentage of 90.98% (79.57%-95.24%) unique tumor neoantigens, while metastases had 86.03% (77.45%-97.14%). For those with liver metastases, the median unique percentage of tumor neoantigens was 80.58% (74.03%-88.66%) in primary lesions and 83.35% (78.49%-91.14%) in metastases. Smoking history and histological types had no impact on the discrepancy of TNB (P > 0.05, P > 0.05; respectively). TNB of primary lesions was similar to matched metastases (P = 0.733). However, primary lesions of brain metastases had a significantly higher percentage of unique tumor neoantigen than that of liver metastases (P = 0.025). There is a large percentage of different tumor neoantigens between primary lesions and matched metastases in lung cancer. Whether this discrepancy could affect the efficacy of following personalized vaccine on primary lesions or matched metastases need further investigation.