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e12526 Background: Luminal B breast cancer is always routinely treated with chemotherapy and endocrine therapy but heterogeneous with respect to sensitivity to treatment, identification of patients who may most benefit remains a matter of controversy. Immune-related genes (IRGs) was found to be associated with the prognosis of breast cancer. The aim of this study is to evaluate the impact of IRGs in predicting the outcome of luminal B breast cancer patients. Methods: According to the Metabric microarray dataset also as a training cohort, 488 luminal B breast cancer patients were selected for generation of immune-related gene signature (IRGS). Another independent dataset (n=250) of patients with complete prognostic information was analyzed as a validation cohort. Prognostic analysis was assessed to test the predictive value of IRGS. Results: A model of prognostic IRGS containing 12 immune-related genes was developed. In both training and validation cohorts, IRGS significantly stratified luminal B breast cancer patients into immune low- and high-risk groups in terms of disease free survival (DFS, HR=4.95, 95% CI=3.22-7.62, P

3533 Background: Primary tumor sidedness has been found to be prognostic in colorectal cancer (CRC), with right-sided colon cancer (RCC) having a worse survival than left-sided tumors (LCC), even after controlling for known negative prognostic factors. Our previous proteomic study identified differences in protein profiles between LCC and RCC. Immune-related proteins were found to be up-regulated in LCC while the differentially expressed proteins in RCC were mainly enriched in extracellular matrix-related proteins. Herein we aim to construct a prognostic prediction model for LCC and RCC patients by using immune-related genes (IRGs) and extracellular matrix-related genes (ECMGs). Methods: A total of 1,868 CRC patients with complete follow-up data from 1 training cohort (n = 562) and 3 independent validation cohorts (n = 622, n = 403, n = 281, respectively) were enrolled in our study. Tumors located in the splenic flexure, descending colon, sigmoid colon, and rectum are defined as LCC. In contrast, tumors located in the region from the hepatic flexure to the cecum are defined as RCC. The Least Absolute Shrinkage and Selection Operator (LASSO) algorithm was used to construct the multi-gene signatures. Univariate and multivariate analyses were used to test the prognostic value of these models. Results: Our biomarker discovery effort identified a 9-gene IRGs signature that significantly associated with poor DFS for LCC (HR = 3.46, 95%CI = 2.38-5.01, P < 0.001) and a 21-gene ECMGs signature associated with prognosis for RCC (HR = 4.53, 95%CI = 2.84-7.22, P < 0.001). For LCC, the IRGs signature was significantly correlated with worse prognosis in three independent validation cohort (Validation-1 cohort: HR = 2.08, 95%CI = 1.41-3.09, P < 0.001; Validation-2 cohort: HR = 2.19, 95%CI = 1.26-3.81, P = 0.004; Validation-3 cohort: HR = 2.94, 95%CI = 1.53-5.63, P < 0.001). Similarly, the ECMGs signature also robustly predicted survival for RCC in three independent validation (Validation-1 cohort: HR = 1.86, 95%CI = 1.22-2.83, P = 0.003; Validation-2 cohort: HR = 1.96, 95%CI = 1.18-3.26, P = 0.008; Validation-3 cohort: HR = 2.8, 95%CI = 1.27-6.17, P = 0.007). When compared with Oncotype DX, we found IRGs achieved an improved survival correlation in LCC (C-index, validation-3 cohort: 0.75 vs 0.64) and ECMGs got a better survival correlation in RCC (C-index, validation-3 cohort: 0.74 vs 0.58). Conclusions: Combing a 9-gene IRGs signature for LCC and a 21-gene ECMGs signature for RCC, we established a prognostic model that can robustly stratify CRC patients into high- and low- risk groups of tumor recurrence and predict prognosis.

e15057 Background: Loss of function mutations for Janus kinases 1/2 (JAK1/2) have shown to be the underling mechanism of primary resistance to immune checkpoint inhibitors (ICIs). However, the correlation between JAK1/2 expression and immune-related genes have not been studied. Methods: Survival, mRNA expression and whole-exome sequencing data from 32 pan-cancer atlas studies were obtained from The Cancer Genome Atlas (TCGA). Correlations between JAK1/2 expression and immune-related genes were depicted in heatmaps. We also analyzed the association between JAK2 gene variants and JAK2 expression. Results: In total, 10071 samples with mRNA expression data were included for analysis. Expression of 46 immune-related genes were positively correlated with JAK2 expression in 25 tumors instead of JAK1 expression. Patients with higher expression of JAK2 had better prognosis than patients with lower expression of JAK2 in 13 tumors. Among 10071 patients, 363 (3.60%) patients harbored JAK2 variants, including 8 with frame shift mutations, 44 with nonsense mutations, 142 with missense mutations, 11 with splices, 8 with fusions, 90 with copy-number reduction and 116 with copy-number amplification. There was no difference in JAK2 expression between patients with JAK2 variants and those without JAK2 variants. However, JAK2 fusion (2.20%, 8/363) and amplification (31.96%, 116/363) were associated with higher JAK2 expression. Conclusions: Our pan-cancer analysis found that JAK2 expression was correlated with immune-related genes and the prognosis of cancer patients. JAK2 fusion and amplification increased the expression of JAK2. Altogether, patients with high JAK2 expression may benefit from ICIs.

e21056 Background: Understanding the genomic landscape of immune-related genes (IRGs) of patient with Non-Small Cell Lung Carcinoma (NSCLC) may provide critical insight and facilitate development of novel strategies for cancer therapy. Methods: Targeted next generation sequencing (NGS) was performed on tissue obtained from patients with NSCLC using a 381-gene panel. The IRGs were mainly based on a published article that summarized the genes related to activated T cells, immune cytolytic activity and IFN-γ release. Genomic alterations including single nucleotide variation (SNV), insertions/deletions, copy number variations (CNV) and gene fusions were assessed. Mutational profiles of IRGs and its correlations with Tumor mutation burden (TMB) and PD-L1 expression in NSCLC patients were analyzed from the 3D Medicine database. Results: Genomic data of 2,510 patients with NSCLC were analyzed via tissue detection [median age 62 years, (IQR: 54 - 69 years)]. 4.26% (107 / 2,510) of the patients had at least one characterized altered IRGs. The most frequently mutated IRGs identified for all genomic alternations occurred in PDCD1LG2 (40%), FAS (27%), LCK (23%), CD274 (21%), CD74 (3%), and missense mutations were the mainly mutant types of PDCD1LG2 and LCK, and copy number gains were showed in PDCD1LG2 and CD274. TMB levels in NSCLC patients with IRGs mutations were higher than in wild-type patients (mean TMB: 14.17 mut/MB vs 9.27 mut/MB, P < 0.001). 65.42% (70/107, 9.35% for PD-L1 > = 1% and < 5%, 28.97% for PD-L1 > = 5% and < 50%, 27.10% for PD-L1 > = 50%) of patients harboring PD-L1-positive ( > = 1%), and the proportion of patients with mutations in IRGs does not exceed 10% in each subgroup. Results of Pearson Chi-square test showed that the PD-L1 expression had different between two groups ( Χ2 = 13.3774, P = 0.0038), patients harboring IRGs mutation had a significantly higher level of PD-L1 than those wide-type patients (P = 0.001). Conclusions: Genomic landscape of IRGs significantly correlated with that of PD-L1 expression. Further analyses using more precisely IRGs and different stage NSCLC samples are requisite to support a role for IRGs as an target to immune therapy of cancers.

3586 Background: Immune-related genes (IRGs) were found to be associated with the prognosis of colorectal cancer (CRC) patients. The aim of this study was to evaluate the impact of IRGs in predicting prognosis of early-stage CRC patients. Methods: According to the CIT microarray data set, 309 early-stage CRC patients were selected for generation of immune-related gene signature (IRGS). 5 independent data sets included 1587 CRC patients with complete prognostic information were divided into a training cohort (566 patients) and two validation cohorts (624 patients in validation-1 and 397 patients in meta-validation). Prognostic analysis were performed to test the predictive value of IRGS. Results: Of 309 early-stage CRC patients, a prognostic immune signature included 23 immune-related genes was constructed. In the training cohort, when considering patients with early tumor stage (I or II), IRGS significantly stratified patients into immune low- vs high-risk groups in terms of disease-free survival (HR = 5.03, 95%CI = 2.94-8.62, P < 0.001). Similarly, higher IRGS was correlated with significantly worse prognosis of early-stage CRC patients in validation-1 (HR = 2.71, 95%CI = 1.44-5.08, P = 0.001) and meta-validation cohort (HR = 3.10, 95%CI = 1.60-6.00, P < 0.001). When compared with Oncotype DX, we found IRGS achieved an improved survival correlation in the training cohort (mean C-index, 0.85 vs 0.65) and the validation-1 cohort (mean C-index, 0.72 vs 0.61). After integrated with clinical characteristics, IRGS remained as an independent prognostic factor after adjusting for T stage and TNM stage of tumor in multivariate analysis (HR = 2.02, 95%CI = 1.61-2.53, P < 0.001). Furthermore, IRGS stratified immune low-risk group patients with adjuvant chemotherapy showed even worse disease-free survival when compared with those without adjuvant chemotherapy (HR = 5.66, 95%CI = 3.153-10.16, P < 0.001 in the training cohort and HR = 3.21, 95%CI = 1.74-5.92, P < 0.001 in the validation-1 cohort). IRGS identified immune high-risk group obtained a significantly higher immune and stromal infiltration (P < 0.001). Particularly, the percentages of Macrophages M2 and CD8+ T cells infiltration were significantly different between these two groups. Conclusions: The proposed prognostic IRGS is a promising system for estimating DFS of colorectal cancer patients, especially those in early-stage. Further studies are needed to evaluate the clinical utility of this system in predicting prognosis of colorectal cancer patients.

e24260Background: Tumor cells altered certain immune related genes to mimic the function of immune cells, which involving in tumor development and having impact on patient's survival. Though the im...

7011 Background: AML LSC are believed to be responsible for residual and resistant leukemic disease leading to relapse. Understanding differences between bulk AML and the LSC subpopulation may allow the identification of novel LSC targets, especially for the most adverse risk AML where few patients are cured. Targeting LSC may be needed to eradicate AML, and immune-based therapies provide an approach for eliminating LSC. The transcriptional landscape of immune-related genes in LSC is not well understood. Methods: Samples were collected at diagnosis from 12 patients with high-risk AML prior to therapy. Bulk (CD45-dim blasts) and LSC (Lin-CD34+CD38-CD123+) AML marrow cells were FACS-sorted and analyzed using whole genome RNA-sequencing. Transcriptomes were analyzed using AltAnalyze software to identify differentially expressed genes in bulk AML cells and in AML LSC populations. These genes were further assessed by gene enrichment analysis using data from Gene Ontology (GO) and the Cancer Genome Atlas Project (CGAP). Results: Sixty-eight genes were identified with greater than 3-fold differential expression between bulk AML and LSC. GO enrichment analysis demonstrated more than 10-fold enrichment of genes involved in the molecular functions, biologic processes, and cell components related to the antigen presentation pathway, with the comparative down-regulation occurring in LSC. Among the top differentially expressed gene clusters, both the MHC class II and interferon-gamma signaling/response pathway gene expression was blunted in LSC. Additional expression analysis revealed that 42% of a CGAP-curated list of 201 antigen-processing and -presentation genes had significantly decreased expression in the LSC subpopulation compared to bulk AML. Conclusions: LSC from primary AML patient samples are characterized by reduction in expression of MHC class II receptor and antigen presentation genes compared to bulk AML. These results suggest that impairment in the presentation and/or processing of tumor associated antigens by MHC class II on LSC, along with tonic sponging of immune response cells and diversion away from LSC by bulk AML, may contribute to LSC evasion of immune surveillance and response.

11613 Background: The antitumor activity of cetuximab (cet) may be affected by extracellular immune mechanisms. We have reported that immune-related genes are associated with survival in mCRC patients (pts) treated with cet (ASCO 2016 abstract#11591). NLR reflects cancer-related inflammation and is a validated prognostic maker in many types of cancers; however, it is not currently used for treatment decision-making. The association between NLR and clinical outcome of cet treatment for mCRC is unknown, and which genes are affecting the NLR remain to be identified. Methods: We enrolled 77 pts (57% males and 15% right-colon cancer) with KRAS exon 2 wild-type from 2 phase II trials (JACCRO CC-05 or CC-06) of 1st-line therapy with FOLFOX or SOX plus cet. All patients’ tissues were measured for expression levels of 354 immune-related genes by HTG EdgeSeq Oncology Biomarker Panel using next generation sequencing for quantitative analysis of targeted RNAs. The association between the NLR and clinical outcome was evaluated using Spearman’s rank correlation coefficient. In addition, the two-sample t-test was performed to investigate which genes had significantly different expression level between NLR-low and high groups in top 100 genes associated with survival among all measured genes. Results: Seventy-one of 77 pts were available for NLR data. The NLR was associated with progression-free survival (PFS) and overall survival (OS) (r = 0.24; p= 0.04, r = 0.29; p= 0.01, respectively). When stratified by median value of NLR, the Kaplan-Meier curve of NLR-low (n = 36) vs. high (n = 35) had a significant difference in both PFS (median 11.8 vs. 9.1 m, p= 0.036) and OS (median 42.8 vs. 26.7 m, p= 0.029). The two-sample t-test revealed that LYZ, TYMP, and CD68 genes expressed significantly differently between NLR-low and high groups (t-test p-value < 0.005, FDR p-value < 0.150). Conclusions: NLR is significantly associated with survival of 1st-line cet treatment for mCRC. Genes encoding for activities on tissue macrophages and endothelial cells may affect the level of NLR associated with outcome of cet combination chemotherapy. Clinical trial information: UMIN000010635.

3038Background: Anti-PD1/PDL1 drugs show consistent activity across various solid tumors. However, a substantial proportion of patients show primary resistance, and those who benefit do not benefit...

6056Background: Immune-related gene expression signatures as candidate predictive biomarkers for cisplatin (CDDP)- and mitomycin C (MMC)-based chemoradiation (CRTX) were established in oropharyngea...

11591Background: CRC Subtyping Consortium identified 4 molecular subtypes, one of which was classified by factors including activation or expression of immune-related pathways (Guinney J, et al. Na...