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Intratumoral Immune Response to Gastric Cancer Varies by Molecular and Histologic Subtype
- Source :
- Am J Surg Pathol
- Publication Year :
- 2019
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2019.
-
Abstract
- BACKGROUND: Immune checkpoint inhibition is effective in a subset of patients with advanced gastric cancer. Genomic profiling has revealed the heterogeneity of gastric adenocarcinomas, but the immune microenvironment and predictors of immunotherapy response remain poorly understood. We aimed to better characterize the underlying immune response to gastric cancer. METHODS: Retrospective review of a prospectively maintained institutional database was performed to identify patients who underwent curative intent resection of gastric adenocarcinoma from 2006–2016. Tumors were classified according to modified TCGA subtype: Epstein-Barr virus-associated (EBV), microsatellite instability-high (MSI), intestinal as a surrogate for chromosomal instability (CIN), diffuse as a surrogate for genomically stable (GS). Tumor infiltrating leukocytes (TIL) were measured using immunohistochemistry. RESULTS: Forty-three patients were identified: 6 EBV, 11 MSI, 14 intestinal, 12 diffuse. The most prevalent TIL were CD8(+) T lymphocytes and CD68(+) macrophages, comprising 15% and 13% of all tumor cells. EBV and MSI tumors were the most infiltrated, harboring 30–50% T cells and 20% macrophages. Intestinal tumors contained fewer T cells but disproportionately more macrophages. Diffuse tumors were the least infiltrated. Programmed cell death protein 1 (PD1) was most frequently expressed in intestinal tumors, whereas 70% of EBV and MSI tumors expressed programmed death-ligand 1 (PDL1). CONCLUSION: We herein demonstrate a heterogeneous immune response to gastric cancer, which varies by tumor subtype and has implications for future immunotherapy trials. Checkpoint inhibition is unlikely to be effective as single-agent therapy against intestinal and diffuse tumors lacking prominent T cell infiltration or substantial PDL1 expression.
- Subjects :
- Adult
Male
0301 basic medicine
Herpesvirus 4, Human
Databases, Factual
medicine.medical_treatment
Programmed Cell Death 1 Receptor
Adenocarcinoma
Article
Pathology and Forensic Medicine
Genetic Heterogeneity
Young Adult
03 medical and health sciences
Lymphocytes, Tumor-Infiltrating
0302 clinical medicine
Immune system
Stomach Neoplasms
Biomarkers, Tumor
Tumor Microenvironment
medicine
Humans
Genetic Predisposition to Disease
Aged
Retrospective Studies
Aged, 80 and over
Tumor microenvironment
CD68
business.industry
Macrophages
Microsatellite instability
Immunotherapy
Middle Aged
medicine.disease
Immune checkpoint
Phenotype
030104 developmental biology
030220 oncology & carcinogenesis
Cancer research
Immunohistochemistry
Female
Microsatellite Instability
Tumor Escape
Surgery
Anatomy
business
CD8
Subjects
Details
- ISSN :
- 01475185
- Volume :
- 43
- Database :
- OpenAIRE
- Journal :
- American Journal of Surgical Pathology
- Accession number :
- edsair.doi.dedup.....688de33ca2de261d92ed462621de69c0