Abstract 88P
Background
It is now clear that the immune system has a substantial effect on the progression of colon cancer. Typically, an immune response defined by a polarized Th1 phenotype, characterized by expression of CXCR3/CCR5 chemokine-receptor ligands, activation of interferon stimulated genes and production of cytotoxic molecules by effector immune cells, has been associated with immune-mediated tumor rejection. We have previously introduced a gene signature, called Immunology Constant of Rejection (ICR), that reflects these immune components. This signature was able to differentiate quite well the patients with an active immune environment and improved survival vs those who did not display this phenotype. This phenomenon although expected based on other immune infiltration studies could not be observed in the TCGA colon cancer cohort, likely due to the per protocol exclusion of samples with low purity. To gain more insight in the underlying mechanism of cancer tissue rejection by the immune system, we build an extensive data repository from high quality colon cancer samples unbiased for tumor purity.
Methods
RNA and DNA were isolated from fresh frozen tissue samples of a cohort of 366 colon cancer patients collected over the last decade at the University of Leiden, Netherlands. Tissue sections flanking the corresponding samples were hematoxylin and eosin stained. RNA-seq (HiSeq4000) data was obtained using HISAT2 alignment and quantile normalization of the GC corrected raw counts. Whole Exome Sequencing (>100X) for our cohort for normal and cancer tissue respectively. T-cell repertoire profiling of 150 tumors was achieved using Adaptive immunoSEQ. Tumor immune phenotype classification was done using unsupervised consensus clustering based on the expression of ICR genes.
Results
Our preliminary data supports a positive impact of ICR gene expression in our colon cancer cohort: patients in ICR High cluster had a significantly improved survival compared to other clusters.
Conclusions
This newly generated immune centric NGS dataset, generated in Qatar, will is used to elucidate the genetic determinants of immune phenotype in colon cancer and the relationship of the immune phenotype, the tumors genetics the TCR diversity.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Sidra Medicine.
Funding
Qatar National Research Fund.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
371P - Clinical utility of Encyclopedic tumour analysis to treat patients advanced refractory head and neck cancers
Presenter: Rajnish Nagarkar
Session: Poster display session
Resources:
Abstract
372P - Real-world fusion landscape in advanced Chinese pancreatic cancer using next generation sequecing: A multicenter study
Presenter: Yiyu Shen
Session: Poster display session
Resources:
Abstract
373P - Molecular profiling of non-small cell lung cancer (NSCLC) in Asia with targeted next-generation sequencing (NGS): Interim analysis of a co-operative group study (ATORG-001)
Presenter: Aaron Tan
Session: Poster display session
Resources:
Abstract
374P - Circulating tumour DNA (ctDNA) identifies actionable genetic alterations in Middle Eastern and Asian (MEA) patients diagnosed with carcinoma of unknown primary (CUP)
Presenter: Nir Peled
Session: Poster display session
Resources:
Abstract
375P - Whole-exome sequencing of tumour-only samples reveals the association between somatic alterations and clinical features in pancreatic cancer
Presenter: Huixin Lin
Session: Poster display session
Resources:
Abstract
376P - Adoption of molecular testing in breast cancer in a tertiary care center in a developing country
Presenter: Prasanta Dash
Session: Poster display session
Resources:
Abstract
377P - NGS in advanced NSCLC in a developing country: Ready for prime time?
Presenter: Amrith B P
Session: Poster display session
Resources:
Abstract
378P - Germline BRCA1/2 testing: Trend in Tan Tock Seng Hospital Singapore
Presenter: Chia Wei Lim
Session: Poster display session
Resources:
Abstract
379P - Study of germline mutations in high risk cancer patients from a tertiary care center in India
Presenter: Padmaj Kulkarni
Session: Poster display session
Resources:
Abstract
380P - Ventricular–Subventricular zone involvement: A predictive factor for survival in glioblastoma
Presenter: Vibhay Pareek
Session: Poster display session
Resources:
Abstract