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Histological differentiation impacts the tumor immune microenvironment in gastric carcinoma:Relation to the immune cycle

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World Journal of Gastroenterology 2021年第31期27卷 5259-5271页

作者： Artem Mashukov Dmytro Shapochka Oleksii Seleznov Nazarii Kobyliak Tetyana Falalyeyeva stanislav kirkilevsky Roman Yarema Oksana Sulaieva Department of Oncology Odessa National Medical UniversityOdessa 65082Ukraine Department of Molecular Pathology and Genetics Medical Laboratory CSDKyiv 03022Ukraine Department of Pathology Medical Laboratory CSDKyiv 03022Ukraine Department of Endocrinology Bogomolets National Medical UniversityKyiv 01601Ukraine Biomedicine Educational-Scientific Center"Institute of Biology and Medicine"Taras Shevchenko National University of KyivKyiv 01601Ukraine Department of Thoracic Tumors National Cancer InstituteKyiv 03022Ukraine Department of Oncology and Medical Radiology Danylo Halytsky Lviv National Medical UniversityLviv 79010Ukraine

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.

关键词： Gastric carcinoma Tumor immune microenvironment Tumor infiltrating lymphocytes Tumor associated macrophages

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