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©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
Histological differentiation impacts the tumor immune microenvironment in gastric carcinoma: Relation to the immune cycle
Artem Mashukov, Dmytro Shapochka, Oleksii Seleznov, Nazarii Kobyliak, Tetyana Falalyeyeva, Stanislav Kirkilevsky, Roman Yarema, Oksana Sulaieva
Artem Mashukov, Department of Oncology, Odessa National Medical University, Odessa 65082, Ukraine
Dmytro Shapochka, Department of Molecular Pathology and Genetics, Medical Laboratory CSD, Kyiv 03022, Ukraine
Oleksii Seleznov, Nazarii Kobyliak, Oksana Sulaieva, Department of Pathology, Medical Laboratory CSD, Kyiv 03022, Ukraine
Nazarii Kobyliak, Department of Endocrinology, Bogomolets National Medical University, Kyiv 01601, Ukraine
Tetyana Falalyeyeva, Biomedicine, Educational-Scientific Center, "Institute of Biology and Medicine" Taras Shevchenko National University of Kyiv, Kyiv 01601, Ukraine
Stanislav Kirkilevsky, Department of Thoracic Tumors, National Cancer Institute, Kyiv 03022, Ukraine
Roman Yarema, Department of Oncology and Medical Radiology, Danylo Halytsky Lviv National Medical University, Lviv 79010, Ukraine
Author contributions: All authors participated in the design, interpretation of the studies, analysis of the data, review of the manuscript and have read and approve the final manuscript; Sulaieva O, Kobyliak N, and Kirkilevsky S designed and performed research, analyzed data, performed statistical analysis, and wrote the manuscript; Mashukov A, Shapochka D, and Seleznov O performed research and analyzed data; Yarema R analyzed data and critically reviewed manuscript.
Institutional review board statement: The study protocol was consistent with the guidelines outlined in the Declaration of Helsinki and approved by the Ethics Committee of Medical Laboratory CSD. The only patients who provided written informed consent for participation in research before their surgery were included in the study.
Informed consent statement: Patients were not required to give informed consent to the study because the analysis used anonymous clinical data that were obtained after each patient agreed to treatment by written consent.
Conflict-of-interest statement: We have no financial relationships to disclose.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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:
http://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Nazarii Kobyliak, PhD, Associate Professor, Department of Endocrinology, Bogomolets National Medical University, Pushkinska 22a str., Kyiv 01601, Ukraine.
nazariikobyliak@gmail.com
Received: March 3, 2021
Peer-review started: March 3, 2021
First decision: April 17, 2021
Revised: May 1, 2021
Accepted: August 9, 2021
Article in press: August 9, 2021
Published online: August 21, 2021
Processing time: 167 Days and 18.2 Hours
BACKGROUND
Various histological types of gastric carcinomas (GCs) differ in terms of their pathogenesis and their preexisting background, both of which could impact the tumor immune microenvironment (TIME). However, the current understanding of the immune contexture of GC is far from complete.
AIM
To clarify the tumor-host immune interplay through histopathological features and the tumor immune cycle concept.
METHODS
In total, 50 GC cases were examined (15 cases of diffuse GC, 31 patients with intestinal-type GC and 4 cases of mucinous GC). The immunophenotype of GC was assessed and classified as immune desert (ID), immune excluded (IE) or inflamed (Inf) according to CD8+ cell count and spatial pattern. In addition, CD68+ and CD163+ macrophages and programmed death-ligand 1 (PD-L1) expression were estimated.
RESULTS
We found that GCs with different histological differentiation demonstrated distinct immune contexture. Most intestinal-type GCs had inflamed TIMEs rich in both CD8+ cells and macrophages. In contrast, more aggressive diffuse-type GC more often possessed ID characteristics with few CD8+ lymphocytes but abundant CD68+ macrophages, while mucinous GC had an IE-TIME with a prevalence of CD68+ macrophages and CD8+ lymphocytes in the peritumor stroma. PD-L1 expression prevailed mostly in intestinal-type Inf-GC, with numerous CD163+ cells observed. Therefore, GCs of different histological patterns have specific mechanisms of immune escape. While intestinal-type GC was more often related to PD-L1 expression, diffuse and mucinous GCs possessing more aggressive behavior demonstrated low immunogenicity and a lack of tumor antigen recognition or immune cell recruitment into the tumor clusters.
CONCLUSION
These data help to clarify the links between tumor histogenesis and immunogenicity for a better understanding of GC biology and more tailored patient management.
Core Tip: In this study, we investigated the tumor-host interplay in gastric carcinoma (GC) through the tumor immune cycle concept. Histologically different GCs vary in immunogenicity and differ in tumor-infiltrating lymphocyte and macrophage densities. Intestinal GC demonstrated predominantly inflamed tumor immune microenvironment and frequent programmed death-ligand 1 expression. In contrast, more aggressive diffuse and mucinous GCs possessed low immunogenicity with a lack of cancer antigen recognition and trafficking. These data help to clarify the links between tumor histogenesis and immunogenicity, offering a better understanding of GC biology and the ability to provide more tailored patient management.
