ESMO 2017: Immune Landscape of PanNETs

Immune expression profile analysis determines metastasis-like primary subtype as having immune-high gene expression

Immune profiling of samples obtained from patients with pancreatic neuroendocrine tumours (PanNETs) identified a pattern of gene expression in the metastasis-like primary (MLP) subtype of PanNETs that may inform the use of immunotherapy, according to findings reported at ESMO 2017, the Annual Congress of the European Society for Medical Oncology in Madrid, Spain.

Dr Anguraj Sadanandam of the Institute of Cancer Research (ICR) in Sutton, UK previously developed a PanNETassigner signature which identified 3 molecular subtypes in PanNETs, MLP, intermediate, and insulinoma-like tumours.

The current study, presented by Dr Kate Young of The Royal Marsden NHS Foundation Trust and carried out under the leadership of Dr Sadanandam at the ICR, aimed to profile the immune architecture of 48 PanNET patient samples across these subtypes to determine whether immunotherapy may be a treatment option for some of these patients.

Forty-eight patients with PanNETs were recruited by Prof. Aldo Scarpa at the ARC-Net Research Centre in Verona, Italy. RNA was isolated from fresh frozen tumour samples for immune gene expression profiling using microarray and the nCounter platform (Nanostring Technology). Computational analysis was also performed to assess immune cell enrichment.

Differential expression of immune-related genes demonstrated across subtypes of PanNET tumour samples

The 48 PanNET samples were classified according to the PanNETassigner gene signature and the tumours were categorised into immune high or immune dormant groups based on immune expression profile analysis.

The majority of the MLP subtype tumours were determined as immune high, whereas most of the insulinoma and intermediate samples were immune dormant, although a small proportion of insulinoma samples were classified as immune high, which may reflect the heterogeneity of this tumour, according to the investigators.

Increased expression of CD8B, LAG3, CD38, CXCL10, CXCL9, CCL19, CD28, and CD27 genes was apparent in the MLP subtype as compared to the other subtypes. Some of these genes, such as CD38, CXCL10 are associated with chronic infection, whereas other genes, including LAG3, are markers of T cell exhaustion.

Immune-Landscape-of-PanNETs

Differentially expressed genes.

© Kate Young. 

PD-1 was highly expressed in 2 of 15 samples classified as MLPs, and FOXP3 was highly expressed in a subset of 7 out of 16 MLP samples. PD-L1 expression was heterogeneous in MLP samples but was highly expressed in 7 of 13 insulinomas.

This differential pattern of immune related gene expression is consistent with computational analysis for immune cell enrichment that was done using microarray data on an overlapping cohort of PanNET samples.

Conclusions

The authors concluded that the differential expression of immune related genes was demonstrated across three PanNET subtypes.

Of these, the MLP subtype appears to be associated with an immune high phenotype.

This profiling may aid to inform patient selection approaches for immunotherapy and rational immunotherapy combinations for treating patients with PanNETs.

Disclosure

The study was in part funded by NIHR Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London and also by the Italian Ministry of Research, the Associazione Italiana Ricerca Cancro and the Fondazione Italiana Malattie Pancreas.

Reference

428O – Young K, et al. Immune Landscape of Pancreatic Neuroendocrine Tumours (PanNETs).