Neoantigen Load as a Prognostic and Predictive Marker for Stage II/III Non-Small Cell Lung Cancer in Chinese Patients

Background: Prognosis of stage II/III non–small-cell lung cancer (NSCLC) is unsatisfactory even after complete tumor resection and adjuvant chemotherapy. Tumors with high immunogenicity were defined as “hot tumors” and associated with clinical benefits from immunotherapy. Here we assessed the prognostic and predictive value of immunogenomic signatures and gene mutation characters for stage II/III non-small cell lung cancer in Chinese patients. Methods: Ninety-one paired resected stage II/III NSCLC and normal tissues and peripheral blood samples, including 47 squamous cell lung carcinomas (SCC) and 44 lung adenocarcinomas (ADC), were collected and analyzed using the whole exome sequencing (WES) to identify gene mutation and immunogenomic signatures for association with clinicopathological variables and disease-free survival (DFS). Results: A high number of tumor mutation burden (TMB, > 4 mutations/Mb) was associated with better DFS of NSCLC patients, although there was no such an association in SCC and ADC subgroups. Moreover, higher neoantigen load (NAL, > 2 neoantigens/Mb) exhibited better DFS and survival benefit after adjuvant chemotherapy in a low NAL subgroup of SCC patients but not in ADC subgroup. A high DNA damage repair (DDR) index (gene mutations occurred in at least three different DNA repair pathways) was associated with high NAL numbers and favorable DFS of SCC, but not in ADC patients. However, mutations of individual gene, oncogene pathways, and antigen presentation machinery genes, and human leukocyte antigen (HLA)-I number and HLA-I loss of heterozygosity (LOH) had no prognostic or predictive value for DFS of SCC or ADC patients. Conclusion: Given the present information, NAL was a useful biomarker for lung SCC prognosis and prediction of chemotherapy responses in Chinese patients. Further study with a larger sample size from multiple institutions is needed to confirm these data.