Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 28, 2018; 24(32): 3583-3616
Published online Aug 28, 2018. doi: 10.3748/wjg.v24.i32.3583
Prognostic significance of tumor immune microenvironment and immunotherapy: Novel insights and future perspectives in gastric cancer
Daniela Cornelia Lazăr, Mihaela Flavia Avram, Ioan Romoșan, Mărioara Cornianu, Sorina Tăban, Adrian Goldiș
Daniela Cornelia Lazăr, Ioan Romoșan, Department of Internal Medicine I, University Medical Clinic, University of Medicine and Pharmacy “Victor Babeş”, Timişoara 300041, Timiş County, Romania
Mihaela Flavia Avram, Department of Surgery X, 1st Surgery Clinic, University of Medicine and Pharmacy “Victor Babeş”, Timişoara 300041, Timiş County, Romania
Mărioara Cornianu, Sorina Tăban, Department of Pathology, University of Medicine and Pharmacy “Victor Babeş”, Timişoara 300041, Timiş County, Romania
Adrian Goldiș, Department of Gastroenterology and Hepatology, University of Medicine and Pharmacy “Victor Babeş”, Timişoara 300041, Timiş County, Romania
Author contributions: All the authors contributed equally to this work.
Conflict-of-interest statement: The authors have no conflict of interest to report.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Daniela Cornelia Lazăr, MD, PhD, Lecturer, Department of Internal Medicine I, University of Medicine and Pharmacy “Victor Babeş”, Piata Eftimie Murgu No.2, Timişoara 300041, Timiş County, Romania.
Telephone: +4-256-220484 Fax: +4-256-220484
Received: May 5, 2018
Peer-review started: May 7, 2018
First decision: May 17, 2018
Revised: June 5, 2018
Accepted: June 27, 2018
Article in press: June 27, 2018
Published online: August 28, 2018

Despite a decrease in gastric cancer incidence, the development of novel biologic agents and combined therapeutic strategies, the prognosis of gastric cancer remains poor. Recently, the introduction of modern immunotherapy, especially using immune checkpoint inhibitors, led to an improved prognosis in many cancers. The use of immunotherapy was also associated with manageable adverse event profiles and promising results in the treatment of patients with gastric cancer, especially in heavily pretreated patients. These data have led to an accelerated approval of some checkpoint inhibitors in this setting. Understanding the complex relationship between the host immune microenvironment and tumor and the immune escape phenomenon leading to cancer occurrence and progression will subsequently lead to the identification of prognostic immune markers. Furthermore, this understanding will result in the discovery of both new mechanisms for blocking tumor immunosuppressive signals and pathways to stimulate the local immune response by targeting and modulating different subsets of immune cells. Due to the molecular heterogeneity of gastric cancers associated with different clinico-biologic parameters, immune markers expression and prognosis, novel immunotherapy algorithms should be personalized and addressed to selected subsets of gastric tumors, which have been proven to elicit the best clinical responses. Future perspectives in the treatment of gastric cancer include tailored dual immunotherapies or a combination of immunotherapy with other targeted agents with synergistic antitumor effects.

Keywords: Immunotherapy, Prognostic significance, Tumor immune microenvironment, Immune checkpoint inhibitors, Gastric cancer

Core tip: The use of modern immunotherapy, including adoptive cell therapy, vaccines, and especially immune therapy using checkpoint inhibitors, has led to encouraging results in clinical trials including gastric cancer patients. This review analyzes the relationship between immune microenvironment profile of the host and tumor development, identification of the immune prognostic markers and future perspectives of immunotherapeutic strategies. The treatment algorithm should be adapted to the specific molecular profile of the gastric cancer subtype in order to obtain maximum clinical benefits.