title: Concordance of immune checkpoints within tumor immune contexture and their prognostic significance in gastric cancer.
abstract: Checkpoint blockade therapy has emerged as a novel approach for cancer immunotherapy in several malignancies. However, patient prognosis and disease progression relevant to immune checkpoints in gastric tumor microenvironment are not defined. This study aims to investigate the expression and prognostic significance of immune checkpoints within gastric cancer. In the study, a cohort of 398 cancer tissues from stage I to IV gastric cancer patients were assessed for programmed cell death 1 ligand 1 (PD-L1) expression and tumor-infiltrating lymphocyte (TIL) infiltration using immunohistochemistry to ascertain their survival correlation. The data revealed that higher TIL density correlated with less risk of disease progression, and exhibited survival benefits in gastric cancer patients, and PD-L1 positivity showed a significant association with the presence of high TIL infiltration. Furthermore, real-time quantitative polymerase chain reaction was performed to detect expression of multiple immune checkpoints with the relation to clinical outcome in 139 samples randomly selected from the same cohort, and higher messenger RNA levels of most immune checkpoints were associated with favorable outcome, while consistently showing a positive correlation with interferon gamma levels. In situ hybridization was used to determine the localization of Epstein-Barr virus (EBV) in 97 specimens, and showed EBV-positive gastric cancer samples correlated with PD-L1 expression and increased TIL density. These results suggest that induction of immune checkpoint within gastric cancer patients reflects a high immune infiltration density, especially in those with EBV-associated gastric cancer, which may direct patient selection for checkpoint blockade therapy.
authors.affiliation: Department of Oncology, Shanghai East Hospital, Tongji University, Shanghai, 200120, China.
authors.forename: Congqi
authors.initials: C
authors.lastname: Dai
authors.affiliation: International Medical Services, Peking Union Medical College Hospital, Beijing, China.
authors.forename: Ruixuan
authors.initials: R
authors.lastname: Geng
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Chenchen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Global Early Development, Merck Serono China, Beijing, China.
authors.forename: Angela
authors.initials: A
authors.lastname: Wong
authors.affiliation: Global Early Development, Merck Serono China, Beijing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Qing
authors.affiliation: Global Early Development, Merck Serono China, Beijing, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Hu
authors.affiliation: Global Early Development, Merck Serono China, Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Division of Anatomical Pathology, Department of Pathology & Clinical Biochemistry, Queen Mary Hospital, Hong Kong Special Administrative Region.
authors.forename: A W I
authors.initials: AW
authors.lastname: Lo
authors.affiliation: Department of Oncology, Shanghai East Hospital, Tongji University, Shanghai, 200120, China. Electronic address: tianyoulijin@163.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Li
mesh_terms: D060890:B7-H1 Antigen / Q000032:analysis* / Q000276:immunology; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000175:diagnosis; D005260:Female; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D006801:Humans; D007150:Immunohistochemistry; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000473:pathology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D013270:Stomach / Q000276:immunology / Q000473:pathology* / Q000821:virology; D013274:Stomach Neoplasms / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology / Q000821:virology*; D016019:Survival Analysis
chemical_list: D060890:B7-H1 Antigen
keywords: Gastric carcinoma; Immune checkpoint; Prognosis; Programmed cell death 1 ligand 1; Tumor-infiltrating lymphocytes