American Association for Cancer Research
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Supplementary Table from Systematic Evaluation of the Immune Environment of Small Intestinal Neuroendocrine Tumors

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posted on 2023-03-31, 23:42 authored by Clare Vesely, Yien Ning Sophia Wong, Alexa Childs, Ayse U. Akarca, Pawan Dhami, Heli Vaikkinen, Lucia Conde, Javier Herrero, Olagunju Ogunbiyi, Amir Gander, Tu Vinh Luong, Chrissie Thirlwell, Martyn Caplin, Christos Toumpanakis, Karl Peggs, Sergio A. Quezada, Teresa Marafioti, Tim Meyer
Supplementary Table from Systematic Evaluation of the Immune Environment of Small Intestinal Neuroendocrine Tumors


NIHR Experimental Cancer Medicine Center




The immune tumor microenvironment and the potential therapeutic opportunities for immunotherapy in small intestinal neuroendocrine tumors (siNET) have not been fully defined. 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. In addition, matched FFPE tissue was obtained for multi-parametric IHC to determine the relative abundance and distribution of T-cell infiltrate. Tumor mutational burden (TMB) was also assessed and correlated with immune infiltration. Effector tumor-infiltrating lymphocytes (TIL) had a higher expression of PD-1 in the tumor microenvironment compared with the periphery. In addition, CD8+ TILs had a significantly higher co-expression of PD-1/ICOS and PD-1/CTLA-4 (cytotoxic T lymphocyte antigen-4) and higher levels of PD-1 expression compared with normal tissue. IHC revealed that the majority of cases have ≤10% intra-tumoral T cells but a higher number of peri-tumoral T cells, demonstrating an “exclusion” phenotype. Finally, we confirmed that siNETs have a low TMB compared with other tumor types in the TCGA database but did not find a correlation between TMB and CD8/Treg ratio. 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 tumor microenvironment to treat patients with siNETs.

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