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Publication Detail
Systematic Evaluation of the Immune Environment of Small Intestinal Neuroendocrine Tumours
  • Publication Type:
    Journal article
  • Authors:
    Vesely C, Wong YNS, Childs A, Akarca AU, Dhami P, Vaikkinen H, Conde L, Herrero J, Ogunbiyi O, Gander A, Luong TV, Thirlwell C, Caplin M, Toumpanakis C, Peggs K, Quezada SA, Marafioti T, Meyer T
  • Publication date:
    23/03/2022
  • Journal:
    Clinical Cancer Research
  • Medium:
    Print-Electronic
  • Status:
    Accepted
  • Country:
    United States
  • PII:
    688114
  • Language:
    English
  • Notes:
    © The Author 2022. This work is licensed under a Creative Commons Attribution International 4.0 License (https://creativecommons.org/licenses/by/4.0/).
Abstract
BACKGROUND: The immune tumour microenvironment and the potential therapeutic opportunities for immunotherapy in small intestinal neuroendocrine tumours (siNET) have not been fully defined. METHODS: Herein, we studied 40 patients with primary and synchronous metastatic siNETs , and matched blood and normal tissue obtained during surgery. We interrogated the immune checkpoint landscape using multi-parametric flow cytometry. Additionally, matched FFPE tissue was obtained for multi-parametric immunohistochemistry (IHC) to determine the relative abundance and distribution of T-cell infiltrate. Tumour mutational burden (TMB) was also assessed and correlated with immune infiltration. RESULTS: Effector tumour infiltrating lymphocytes had a higher expression of PD-1 in the tumour microenvironment compared to the periphery. Additionally, CD8+ tumour infiltrating lymphocytes had a significantly higher co-expression of PD-1/ICOS and PD-1/CTLA-4 and higher levels of PD-1 expression compared to normal tissue. IHC revealed that the majority of cases have {less than or equal to}10% intratumoural T cells but a higher number of peritumoural T cells, demonstrating an "exclusion" phenotype. Finally, we confirmed that siNETs have a low TMB compared to other tumour types in the TCGA database but did not find a correlation between TMB and CD8/Treg ratio. CONCLUSIONS: Taken together, these results suggest that a combination therapy approach will be required to enhance the immune response, using PD-1 as a checkpoint immunomodulator backbone in combination with other checkpoint targeting molecules (CTLA-4 or ICOS), or with drugs targeting other pathways to recruit "excluded" T cells into the tumour microenvironment to treat patients with siNETs.
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