Open Access

Tumor microenvironment immune types in gastric cancer are associated with mismatch repair however, not HER2 status

  • Authors:
    • Anna Maria Valentini
    • Federica Di Pinto
    • Sergio Coletta
    • Vito Guerra
    • Raffaele Armentano
    • Maria Lucia Caruso
  • View Affiliations

  • Published online on: June 21, 2019     https://doi.org/10.3892/ol.2019.10513
  • Pages: 1775-1785
  • Copyright: © Valentini et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The treatment of patients with human epidermal growth factor receptor 2 (HER2)‑negative gastric cancer is a major challenge. Immunotherapy using immune checkpoint inhibitors is a rapidly growing field. In a number of malignancy types it has been demonstrated that patients with mismatch repair deficiency efficiently respond to programmed death‑ligand 1 (PD‑L1) blockade therapy. Recent studies have evaluated tumor microenvironment immune types to predict which patients may clinically benefit from immunotherapy. The present study aimed to evaluate the immunohistochemical expression of PD‑L1 in 70 gastric cancer tissue samples. Potential associations between PD‑L1 expression and mismatch repair deficiency, HER2 and Epstein Barr virus (EBV) status were then investigated in the context of the tumor microenvironment. A positive association was identified for PD‑L1 expression with mismatch repair deficiency and EBV status; however, no association was revealed with HER2 status. Immunohistochemistry was then used to classify the microenvironment immune types. This demonstrated that the majority of the gastric cancer samples (73%) belonged to the tumor microenvironment immune type II [PD‑L1‑/cluster of differentiation 8 (CD8)+ low], which involves an immune ignorant state and has a low sensitivity to immunotherapy. However, 7% of the gastric cancer cases were identified to belong to the tumor microenvironment immune type I (PD‑L1+/CD8+ high), which exhibits adaptive immune escape responses and a high chance of reversion with immune checkpoint blockade therapy. In conclusion, the present study emphasized the importance of evaluating tumor microenvironment immune types, mismatch repair deficiency status and EBV status, rather than PD‑L1 expression alone, when evaluating the eligibility of a patient for immunotherapy with anti‑programmed cell death protein‑1/PD‑L1 antibodies.
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August-2019
Volume 18 Issue 2

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Valentini AM, Di Pinto F, Coletta S, Guerra V, Armentano R and Caruso ML: Tumor microenvironment immune types in gastric cancer are associated with mismatch repair however, not HER2 status. Oncol Lett 18: 1775-1785, 2019.
APA
Valentini, A.M., Di Pinto, F., Coletta, S., Guerra, V., Armentano, R., & Caruso, M.L. (2019). Tumor microenvironment immune types in gastric cancer are associated with mismatch repair however, not HER2 status. Oncology Letters, 18, 1775-1785. https://doi.org/10.3892/ol.2019.10513
MLA
Valentini, A. M., Di Pinto, F., Coletta, S., Guerra, V., Armentano, R., Caruso, M. L."Tumor microenvironment immune types in gastric cancer are associated with mismatch repair however, not HER2 status". Oncology Letters 18.2 (2019): 1775-1785.
Chicago
Valentini, A. M., Di Pinto, F., Coletta, S., Guerra, V., Armentano, R., Caruso, M. L."Tumor microenvironment immune types in gastric cancer are associated with mismatch repair however, not HER2 status". Oncology Letters 18, no. 2 (2019): 1775-1785. https://doi.org/10.3892/ol.2019.10513