Abstract
e20034 Background: Previous attempts to define tumor immune environment in non-small cell lung cancer (NSCLC) did not present comprehensive analyses. We established immunogenomic profiling project of NSCLC (ICON) to integrate immune, proteomic, genomic, transcriptomic, demographic, clinical, pathologic, and outcome data from surgically resected lung cancers. Methods: Tumor, normal lung tissue, and blood are collected at the time of surgery and blood after surgery up to 1 year. Samples are processed for tumor infiltrating lymphocyte (TILs) isolation and expansion; generation of patient derived xenografts (PDX), immunohistochemical (IHC) evaluation of immune cells and markers, genomic and proteomic analyses. Results: 73 (75%) out of 98 enrolled patients, median age 66 years, contributed samples to ICON; 33 (46%) males, 62 (85%) former smokers, 11 (15%) never smokers. 50 (68%) had adenocarcinoma, 17 (23%) squamous cell carcinoma, 3 (4%) small cell, and 3 (4%) pleomorphic carcinoma. 30 (41%) had stage I, 28 (38%) stage II, and 14 (19%) stage III disease, and one stage 4; 9 (12%) patients received neoadjuvant chemotherapy. Median tumor size was 4.0 cm and 67 (92%) underwent R0 resection. TIL expansion was successful in 47/67 (70%) cases. Phenotypic and functional analysis of freshly isolated and cultured TIL is ongoing. Preliminary results show suppression of intratumoral CD8+ cells as demonstrated by low perforin (p = 0.0002) and high CD8+ PD1 (p = 0.0007) levels as compared to normal tissue; however tumor CD8+CD28 co-stimulatory molecule expression was high p = 0.0003. PDX success rate has been 27%. IHC analyses show higher CD8+PD1, CD3, CD8+BTLA expression in SCC than in adenocarcinoma (p = 0.05). Exome sequencing and RNA sequencing from 19 patients show median mutation burden 466/tumor. Subclonal analysis, neoantigen prediction and expression status of predicted neoantigens are ongoing. Conclusions: ICON is an ambitious multi-team project designed to integrate wide range of tumor related data. Preliminary analysis demonstrates the project to be feasible with high rate of data acquisition. Tumors profiled from ICON will serve as a reference for the upcoming neoadjuvant single and dual checkpoint immunotherapy trial.
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