Cytolytic activity score as a biomarker for antitumor immunity and clinical outcome in patients with gastric cancer.

Abstract

BACKGROUND:

A simple measure of immune cytolytic activity (CYT) base on mRNA expression levels of two genes, GZMA and PRF1, was recently reported. Here, we aimed to evaluate the CYT score's potential as a measure of antitumor immunity and predictor of clinical outcome in gastric cancer (GC) patients.

MATERIALS AND METHODS:

We evaluated the correlations between tumor-infiltrating immune cells and the CYT score in 238 GC samples from The Cancer Genome Atlas (TCGA). Next, we investigated CYT score associations with molecular subtypes, somatic mutation load, and immune checkpoint molecules in GC samples from TCGA and Asian Cancer Research Group (ACRG). Moreover, we evaluated the clinical significance of the CYT score calculated by reverse transcription (RT)-quantitative PCR (qPCR) data in 123 GC samples and the association of the CYT score with the response to anti-PD-1 therapy in 7 GC samples from Kyushu University Hospital.

RESULTS:

The CYT score positively correlated with the proportions of tumor-infiltrating CD8+ T cells and macrophages and negatively correlated with the proportion of regulatory T cells in GC tissues. A high CYT score was associated with common immune checkpoint molecules, a high mutation, the Epstein-Barr virus subtype, and the microsatellite instability subtype in GC. Moreover, a low CYT score was a poor prognosis factor in patients with GC. Finally, the CYT score was higher in a responder to anti-PD-1 therapy compared to nonresponders.

CONCLUSION:

The CYT score reflects antitumor immunity and predicts clinical outcome in GC patients.

• Authors: Qingjiang Hu, Kentaro Nonaka, Hiroaki Wakiyama, Yu Miyashita, Yoshiaki Fujimoto, Tomoko Jogo, Kentaro Hokonohara, Ryota Nakanishi, Yuichi Hisamatsu, Koji Ando, Yasue Kimura, Takaaki Masuda, Eiji Oki, Koshi Mimori, Yoshinao Oda, Masaki Mori
• Journal: Cancer medicine (Cancer Med) Vol. 10 Issue 9 Pg. 3129-3138 (05 2021) ISSN: 2045-7634 [Electronic] United States
• PMID: 33769705 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Chemical References

• Biomarkers, Tumor
• Immune Checkpoint Inhibitors
• Immune Checkpoint Proteins
• PRF1 protein, human
• RNA, Messenger
• Perforin
• Granzymes
• GZMA protein, human

Topics

• Aged
• Biomarkers, Tumor (immunology)
• CD8-Positive T-Lymphocytes (cytology, immunology, metabolism)
• Cohort Studies
• Databases, Genetic
• Female
• Granzymes (genetics, metabolism)
• Humans
• Immune Checkpoint Inhibitors (therapeutic use)
• Immune Checkpoint Proteins (metabolism)
• Immunity, Cellular
• Immunotherapy, Adoptive (methods)
• Lymphocytes, Tumor-Infiltrating (cytology, immunology)
• Male
• Mutation (immunology)
• Perforin (genetics, metabolism)
• Prognosis
• RNA, Messenger (metabolism)
• Stomach Neoplasms (genetics, immunology, therapy)
• T-Lymphocytes, Regulatory (cytology, immunology)
• Treatment Outcome
• Tumor Microenvironment (immunology)
• Tumor-Associated Macrophages (immunology)