Dataset Information

SLAMF8 expression predicts the efficacy of anti‐PD1 immunotherapy in gastrointestinal cancers

ABSTRACT: Abstract

Objectives

Epstein–Barr virus (EBV) infection is associated with a better response to anti‐PD1 immunotherapy. We hypothesised that genetic alterations induced by EBV infection are responsible for the activation of key immune responses and hence are predictive of anti‐PD1 efficacy.

Methods

With transcriptome data of gastric cancer (GC), we explored differentially expressed genes (DEGs) specific for EBV infection and performed coexpression network analysis using the DEGs to identify the consistent coexpression genes (CCGs) between EBV‐positive and EBV‐negative GC tissues. We selected the tag genes of the CCGs and validated them using RNA sequencing and immunohistochemistry. We established murine models and collected tissues from clinical patients to test the value of SLAMF8 in predicting anti‐PD1 treatment. The location and expression of SLAMF8 were characterised by multiplex immunofluorescence and quantitative PCR. Moreover, exogenous overexpression and RNA‐sequencing analysis were used to test the potential function of SLAMF8.

Results

We identified 290 CCGs and validated the tag gene SLAMF8 in transcriptome data of gastrointestinal cancer (GI). We observed that the T‐cell activation pathway was significantly enriched in high‐expression SLAMF8 GI cancers. Higher SLAMF8 expression was positively associated with CD8 expression and a better response to anti‐PD1 treatment. We further observed dynamically increased expression of SLAMF8 in murine models relatively sensitive to anti‐PD1 treatment. SLAMF8 was mainly expressed on the surface of macrophages. Exogenous overexpression of SLAMF8 in macrophages resulted in enrichment of positive regulation of multiple immune‐related pathways.

Conclusion

Higher SLAMF8 expression may predict better anti‐PD1 immunotherapy efficacy in GI cancer. In this study, we found that SLAMF8 was involved in activating the antitumour immune response in gastrointestinal (GI) cancer. Thus, higher SLAMF8 expression may predict better anti‐PD1 immunotherapy efficacy in GI cancer.

SUBMITTER: Zhang Q

PROVIDER: S-EPMC8546794 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:In this study, a bibliometric analysis was carried out to identify the most influential clinical studies and research trends on anti-programmed cell death 1/programmed cell death 1 ligand 1 (anti-PD1/PDL1) immunotherapy. On January 1, 2022, we used Web of Science to identify the 100 most frequently cited papers on clinical studies investigating anti-PD1/PDL1 immunotherapy, and extracted the following data: publication year, source title, country/region, institution, and the total number of citations. The research design and area were classified independently by the authors. Subsequently, we carried out a bibliometric analysis to determine the trends and identify the major journals on anti-PD1/PDL1 immunotherapy. The authors analyzed the current research hotspots based on papers published in major journals from 2020 to 2021. These 100 papers were cited a total of 138,840 times, and the median number of citations was 899.5 (range: 341-7,983). "Safety, activity, and immune correlates of anti-PD-1 antibody in cancer" by Topalian et al. had the highest number of citations (7,983 times). New England Journal of Medicine had the highest number of top-cited papers (40 papers), average citations per paper (1,558.3 citations), and rate of top-cited papers (65.6%). Authors from the USA contributed most of the papers (76 papers). Lung cancer (30 papers, 46,422 citations) and melanoma (20 papers, 30,881 citations) were the most cited research areas. In summary, anti-PD1/PDL1 has become standard treatment for various cancer, while adjuvant anti-PD1/PDL1 therapy is currently a research hotspot. New England Journal of Medicine was identified as the most influential journal in this area. Non-small cell lung cancer and melanoma are the most well-studied cancers, while nivolumab and pembrolizumab are the most commonly investigated anti-PD1/PDL1 antibodies. Further studies are warranted to identify effective predictive biomarkers or models, clarify the molecular mechanism of combined therapy, and establish optimal therapeutic strategies. This study may assist researchers in obtaining a comprehensive impression of the landscape and current trends in anti-PD1/PDL1 immunotherapy and gain inspiration to conduct further studies.