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Vesely, Clare; Wong, Yien Ning Sophia; Childs, Alexa; Akarca, Ayse U.; Dhami, Pawan; Vaikkinen, Heli; Conde, Lucia; Herrero, Javier; Ogunbiyi, Olagunju; Gander, Amir; Luong, Tu Vinh; Thirlwell, Chrissie; Caplin, Martyn; Toumpanakis, Christos; Peggs, Karl; Quezada, Sergio A.; Marafioti, Teresa; Meyer, Tim

Systematic Evaluation of the Immune Environment of Small Intestinal Neuroendocrine Tumors

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  • Medientyp: E-Artikel
  • Titel: Systematic Evaluation of the Immune Environment of Small Intestinal Neuroendocrine Tumors
  • Beteiligte: Vesely, Clare; Wong, Yien Ning Sophia; Childs, Alexa; Akarca, Ayse U.; Dhami, Pawan; Vaikkinen, Heli; Conde, Lucia; Herrero, Javier; Ogunbiyi, Olagunju; Gander, Amir; Luong, Tu Vinh; Thirlwell, Chrissie; Caplin, Martyn; Toumpanakis, Christos; Peggs, Karl; Quezada, Sergio A.; Marafioti, Teresa; Meyer, Tim
  • Erschienen: American Association for Cancer Research (AACR), 2022
  • Erschienen in: Clinical Cancer Research, 28 (2022) 12, Seite 2657-2668
  • Sprache: Englisch
  • DOI: 10.1158/1078-0432.ccr-21-4203
  • ISSN: 1078-0432; 1557-3265
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: Abstract Purpose: The immune tumor microenvironment and the potential therapeutic opportunities for immunotherapy in small intestinal neuroendocrine tumors (siNET) have not been fully defined. Experimental Design: 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. Results: 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. 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 tumor microenvironment to treat patients with siNETs.
  • Zugangsstatus: Freier Zugang