scholarly journals Immune gene expression profiling (GEP) of resected gastric adenocarcinomas (GAs) to identify biomarkers associated with immune checkpoint inhibitor (ICPI) response in early stage disease

2018 ◽  
Vol 29 ◽  
pp. viii231
Author(s):  
J. Chao ◽  
H. Yin ◽  
J. Lee ◽  
S.J. Klempner ◽  
R. Pillai
Keyword(s):  
Gene Expression ◽  
Expression Profiling ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Early Stage ◽  
Immune Gene ◽  
Early Stage Disease ◽  
Immune Gene Expression ◽  
Gastric Adenocarcinomas ◽  
Stage Disease

Expression of immune genes and a signature of PD-1 inhibition resistance in basal-like pancreatic adenocarcinoma (PDAC) subtypes.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 277-277
Author(s):  
Ranjit Joseph ◽  
Kyla Collins ◽  
Dante S. Bortone ◽  
Benjamin Garrett Vincent ◽  
Jen Jen Yeh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Subtypes ◽  
Checkpoint Inhibitors ◽  
Molecular Subtype ◽  
Early Stage ◽  
Patient Characteristics ◽  
Immune Gene ◽  
Recurrence Rates ◽  
Immune Genes ◽  
Immune Gene Expression

277 Background: PDAC is a lethal disease with poor survival even when detected at an early stage. Recurrence rates after surgical resection remain high. Recently, two distinct molecular subtypes of PDAC (basal-like and classical) have been identified with basal-like tumors demonstrating inferior outcomes. We hypothesize that differences in tumor immunogenicity may contribute to this aggressive biology and predict response to immune checkpoint inhibitors. Methods: RNA sequencing was performed on formalin-fixed paraffin embedded samples of 60 resected PDAC patients. We evaluated previously published immune gene expression signatures comprised of 1400 genes and used a single sample classifier to determine molecular subtypes. Results: Table 1 summarizes patient characteristics in our cohort. There were 35 classical and 25 basal-like tumors. PFS was significantly shorter in patients with basal-like compared to classical subtypes (9 vs 15 mo, p = 0.006). In a multivariable model with molecular subtype, lymph node and margin status, subtype was the only independent predictor of PFS (p=0.028). Unsupervised clustering identified two distinct immune groups that were associated with molecular subtypes (p=0.038) with higher expression of immune genes in basal-like tumors. Basal-like tumors were significantly associated with an immunosuppressive signature (p<0.001) and a signature associated with non-response to PD-1 inhibition in melanoma (p=0.001). Conclusions: This is the first study to show that basal-like pancreatic cancers are associated with increased immune gene expression and may help explain their inferior prognosis. We hypothesize that this reflects an increase in immunosuppressive cells in basal-like tumors that may predict decreased response to immune check point inhibitors. [Table: see text]

scholarly journals Immune gene expression profiling reveals heterogeneity in luminal breast tumors

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Bin Zhu ◽  
Lap Ah Tse ◽  
Difei Wang ◽  
Hela Koka ◽  
Tongwu Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Expression Profiling ◽  
Normal Tissue ◽  
Breast Tumors ◽  
Immune Gene ◽  
Deletion Polymorphism ◽  
Genomic Features ◽  
Immune Gene Expression ◽  
Asian Populations

Abstract Background Heterogeneity of immune gene expression patterns of luminal breast cancer (BC), which is clinically heterogeneous and overall considered as low immunogenic, has not been well studied especially in non-European populations. Here, we aimed at characterizing the immune gene expression profile of luminal BC in an Asian population and associating it with patient characteristics and tumor genomic features. Methods We performed immune gene expression profiling of tumor and adjacent normal tissue in 92 luminal BC patients from Hong Kong using RNA-sequencing data and used unsupervised consensus clustering to stratify tumors. We then used luminal patients from The Cancer Genome Atlas (TCGA, N = 564) and a Korean breast cancer study (KBC, N = 112) as replication datasets. Results Based on the expression of 130 immune-related genes, luminal tumors were stratified into three distinct immune subtypes. Tumors in one subtype showed higher level of tumor-infiltrating lymphocytes (TILs), characterized by T cell gene activation, higher expression of immune checkpoint genes, higher nonsynonymous mutation burden, and higher APOBEC-signature mutations, compared with other luminal tumors. The high-TIL subtype was also associated with lower ESR1/ESR2 expression ratio and increasing body mass index. The comparison of the immune profile in tumor and matched normal tissue suggested a tumor-derived activation of specific immune responses, which was only seen in high-TIL patients. Tumors in a second subtype were characterized by increased expression of interferon-stimulated genes and enrichment for TP53 somatic mutations. The presence of three immune subtypes within luminal BC was replicated in TCGA and KBC, although the pattern was more similar in Asian populations. The germline APOBEC3B deletion polymorphism, which is prevalent in East Asian populations and was previously linked to immune activation, was not associated with immune subtypes in our study. This result does not support the hypothesis that the germline APOBEC3B deletion polymorphism is the driving force for immune activation in breast tumors in Asian populations. Conclusion Our findings suggest that immune gene expression and associated genomic features could be useful to further stratify luminal BC beyond the current luminal A/B classification and a subset of luminal BC patients may benefit from checkpoint immunotherapy, at least in Asian populations.

Different patterns of non immediate allergic reaction to BRAF inhibitor in two patients with metastatic melanoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21052-e21052 ◽  
Author(s):  
Miguel-Angel Berciano-Guerrero ◽  
Rocío Lavado ◽  
Álvaro Montesa ◽  
Martina Alvarez ◽  
Angela Santonja ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lymph Node ◽  
Gene Expression Profiling ◽  
Metastatic Melanoma ◽  
Expression Profiling ◽  
Braf Inhibitor ◽  
Braf V600e ◽  
Immune Gene ◽  
Skin Reactions ◽  
Immune Gene Expression

e21052 Background: Non immediate allergic reactions (niAR) related with oncology drugs are a rare entity. Usually, it is called Drug Reaction with eosinophilia and sistemic symptoms (“DRESS”), occurring at first ten days of treatment.Recently, the treatment of metastatic melanoma (MM) has included new drugs in patients wtih BRAF V600E mutation. Despite skin reactions are usual, niAR to these drugs have not been reported. We present 2 clinical cases with mm treated with BRAFi, developing such niAR. Methods: Patient 1: 47yo female with lymph node relapse and multiple subcutaneous skin metastases (previously pT1N0M0 melanoma) that received nivolumab in adjuvant setting. BRAF-mutated. She starts with Vemurafenib-Cobimetinib (V-C). At 8 days, niAR (maculo-papular exantema G4, fever G2). After discontinuation of this treatment (3 weeks), it is changed to Dabrafenib(50%)-Trametinib (D-T). With only 1 dose, skin niAR (G3) is newly developed. Biopsy are taken at the beginning (T0), during (T1) and after desentizitation (T2). Patient 2: 60 yo female, lung and lymph node relapse of melanoma (previously pT2bN0M0) after IFN-alpha adjuvant 2 years before. BRAF-mutated. Start with V-C. At 9 days, skin niAR (G4), with fever (G1). Discontinuation of treatment. Biopsys and blood test are taken (T0, T1 and T2). Gene expression was performed with PanCancer Immune Profiling Panel Nanostring™ in this points. Results: Different lymphocytic subpopulations in blood and biopsy at acute phase are showed in table 1. Immune gene expression profiling found decreased expression of 5 genes: UBC, IL8, IL32, NFKB1A and FOS, increasing IFNGR1 (pt 1). In both of pts, desensitizitation protocol by Allergologists was made succesfully, with incremental oncology drugs and steroid reduction protocol. Both of pts had a maior partial response (RECIST), even the scarce of the drug received. Conclusions: D and V develop important “of class” skin niAR. Different immunologic patterns are related with this niAR. Previous exposition to IFN or anti-PD1 therapy might modulate such response. Immune gene expression profiling could be used as a method to identify biomarkers. Desensitization with BRAFi has enough efficacy and tolerance.

Identifying predictive biomarkers for metastatic progression in stage I and II clear cell renal cell carcinoma.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 631-631
Author(s):  
Neal J Murphy ◽  
Andrew Shih ◽  
Zachary Kozel ◽  
Paras Shah ◽  
Oksana Yaskiv ◽  
...  
Keyword(s):  
Gene Expression ◽  
Early Stage ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Stage I ◽  
Stage Ii ◽  
Cell Renal Cell Carcinoma ◽  
Early Stage Disease ◽  
Stage Disease ◽  
Experimental Group

631 Background: For most clear cell renal cell carcinoma (ccRCC) patients with early stage disease, surgical resection offers definitive cure. However, for the small percentage of tumors that metastasize, analyzing gene expression profiles from the primary site at the time of nephrectomy can serve as a model to understand the molecular aberrations behind a metastatic phenotype. Differences in gene expression profiles between patients with Stage I and II ccRCC who experience metastasis versus patients who maintain cure after surgery may help elucidate significant molecular targets and stratify patients at higher risk for metastasis. Methods: Nineteen Stage I and twenty Stage II ccRCC tumors preserved in FFPE blocks after nephrectomy were included in this study. Patients were matched for age, gender, tumor size and grade. In both stages, approximately half the patients that experienced metastasis within 5 years of surgery were part of the experimental group, whereas the control group had > 5 years of follow-up without evidence of disease. Extracted RNA for Stage I patients was sequenced using Illumina TruSeq RNA Access Library. Gene counts were assessed by ht-seq counts and differential expression using DESeq2. Significant genes found were validated in the Stage II group using RT-qPCR. Results: In the Stage I experimental group, statistically significant upregulation of several genes associated with unfavorable prognosis in RCC were found: COL1A1, NUMBL, and STEAP3. Random forest classification accurately separated Stage I control versus experimental patients based on expression of COL1A1. Affected genes were consistent with molecular changes seen in TCGA analysis. In the Stage II group, a double-blinded analysis correctly identified the clinical outcome for the majority of the patients using qPCR expression of COL1A1, NUMBL, and STEAP3. Conclusions: Differences in gene expression profiles harbored in the primary site of early stage ccRCC may be employed to predict patients at high risk for developing metastasis. Validating these findings in a larger study carries the potential to better understand mechanisms of metastasis and identify an at risk cohort of patients with early stage disease.

Sign in / Sign up

Export Citation Format

Share Document