Immunotherapy is currently being explored in many tumour types with encouraging results, but has not yet been evaluated in neuroendocrine tumours (NET). Our aim is to characterise the immune landscape of NET and determine which immune-modulatory pathways control the tumour infiltrating lymphocytes (TILs) in order to develop a rational approach for immunotherapy in this tumour type.
Peripheral blood and fresh tissue was obtained from consenting patients with NET, and subjected to multicolour flow-cytometry to determine the abundance of CD8+, CD4+FoxP3- effector (CD4eff) and CD4+FoxP3+ regulatory (Treg) T cell subsets and the expression of co-inhibitory and co-stimulatory checkpoint molecules on these subsets. Additionally, matched FFPE tissue was obtained for multiparametric immunohistochemistry to investigate the distribution of the immune infiltrate.
Tissue from 23 NET patients including 19 mid-gut tumours (13: G1 and 6: G2) was analysed. Overall the tumours contained a higher proportion of Tregs compared with peripheral blood (8.5% vs 5%, P = 0.02) and had a CD8:Treg ratio of 18.1:24.3 respectively (P = 0.036). The co-inhibitory molecules CTLA-4 and TIM-3 showed highest expression on Tregs, while PD-1 and LAG-3 expression was similar across all T cell subsets. Co-stimulatory molecules, including ICOS, 41BB and OX-40, were also highest on Tregs, as was the recently identified co-stimulatory receptor TIGIT. Immunohistochemistry revealed that the majority of cases have
These preliminary results provide novel insight into the immune landscape of NET, and may inform the development of targeted combination immunotherapies. Initial results suggest that checkpoint molecules, such as PD1 and LAG-3, may be potential targets in this tumour type and work is ongoing to further elucidate the immunogenic potential of NET.
Clinical trial identification
Legal entity responsible for the study
University College London
All authors have declared no conflicts of interest.