256 Views
Immuno-oncology
Oral
Khyati Shah
Postdoctoral fellow
UCSF
Phuong Nguyen
Research Officer
Translational Immunology Institute/SingHealth-DukeNUS Academic Medical Centre, Singapore
Siming Ma, PhD
Genome Institute of Singapore (GIS)/Agency for Science, Technology and Research (A*STAR)
Hannah Lai
Genome Institute of Singapore (GIS)/Agency for Science, Technology and Research (A*STAR)
Chun Jye Lim
Translational Immunology Institute, Singhealth/Duke-NUS Academic Medical Centre
Jiaqi Lim
Genome Institute of Singapore (GIS)/Agency for Science, Technology and Research (A*STAR)
Tony Kiat Hon Lim, MD
Department of Pathology/Singapore General Hospital, Singapore
Salvatore Albani
Director
Translational Immunology Institute, Singhealth/Duke-NUS Academic Medical Centre
Pierce Chow, MD PhD
National Cancer Centre Singapore
Weiwei Zhai, PhD
Genome Institute of Singapore (GIS)/Agency for Science, Technology and Research (A*STAR)
Valerie Chew, PhD
Junior PI
Translational Immunology Institute, Singhealth/Duke-NUS Academic Medical Centre
Intratumoural genomic heterogeneity and its implication on tumour evolution and clinical prospect were previously described in various cancers. The degree of intratumoural heterogeneity (ITH) in immune landscapes, the co-evolution between tumour and its immune microenvironment, was however not previously explored. Here, we revealed significant level of immune-ITH and its relationship with tumour evolution by simultaneous single-cell cytometry by time-of-flight (CyTOF), whole genome sequencing (WGS) and RNA sequencing on multiple tumour sectors from resected hepatocellular carcinoma (HCC) (total 95 sectors from 28 patients). Immune-ITH was observed on major immune lineages as well as specific subsets, including regulatory T cells (Treg) and exhausted CD8+ T cells. Remarkably, we found that patients with high immune-ITH had advanced stages of disease, bigger tumour size and a higher risk of recurrence than those with low immune-ITH. High immune-ITH was also characterised by enhanced immunosuppression, exhaustion and reduced infiltration by cytotoxic or activated immune cells showing a reduced immunoselection pressure. Consistently, we found the enhanced neoantigen loads to be linked to high immune-ITH indicating the tumour-immune co-evolution process. In tumours with high immune-ITH, we discovered a unique transcriptomic signature and tumour-immune network associated to disease progression. This transcriptomic signature also correlated to poor overall survival profiles in public HCC cohorts. The in-depth investigation of immune-ITH along with tumour genomics provided a holistic view on the complexity and co-evolution process of tumour-immune interface.