NKG7 is a cytolytic granule-associated protein. The authors show that NKG7 is critical for cytotoxic CD8 + T-cell antitumor activity and that NKG7 mRNA transfection improves cytotoxic CD8 + T-cell tumor-cell killing, identifying NKG7 as a potential therapeutic target.
Background
With the popularity of serum prostate‐specific antigen (PSA) screening, the number of newly diagnosed prostate cancer (PCa) patients is increasing. However, indolent and invasive PCa cannot be distinguished by the PSA level. Here, we mainly explored the role of heterogeneous nuclear ribonucleoprotein M (hnRNPM) in the invasiveness of PCa.
Methods
Reverse‐transcription quantitative polymerase chain reaction and Western blotting were used to detect the expression of hnRNPM in PCa and benign prostate hyperplasia (BPH) tissue samples as well as PCa cell lines. Immunohistochemistry was applied to detect hnRNPM or Yin Yang 1 (YY1) expression in BPH, prostate adenocarcinoma (ADENO) and neuroendocrine prostate cancer (NEPC) tissue samples. After aberrant hnRNPM expression was detected in C4‐2 and PC3 cells, changes in cell migration and invasion were observed through wound healing and transwell assays, respectively. We also predicted the transcription factor (TF) of hnRNPM through databases and then verified the association between hnRNPM and YY1 using chromatin immunoprecipitation and luciferase assays.
Results
The hnRNPM expression pattern exhibited a gradual reduction from BPH tissue to ADENO tissue to NEPC tissue, and hnRNPM had lower expression in more aggressive PCa cell lines. The overexpression of hnRNPM could significantly reduce the expression of Twist1, which inhibits the migration and invasion of PCa cells in vitro. In PCa cells, the overexpression of YY1 could promote epithelial‐mesenchymal transition (EMT) by reducing hnRNPM expression. Furthermore, this effect caused by the overexpression of YY1 could be partially attenuated by the simultaneous overexpression of hnRNPM.
Conclusions
Our study demonstrates that hnRNPM negatively regulates PCa cell migration and invasion, and that hnRNPM expression can be transcriptionally inhibited by YY1. We speculate that hnRNPM may be a biomarker that can assist in assessing PCa aggressiveness.
Immune checkpoint inhibitors (ICIs), as a novel class of anticancer therapy, can be more efficacious and less toxic than chemotherapy, but their clinical success is confined to certain tumor types. Elucidating their targets, mechanisms and scope of action, and potential synergism with chemotherapy and/or targeted therapies are critical to widen their clinical indications. Treatment response to an ICI targeting programmed death‐1 (anti‐PD‐1) is sought to be understood here by conducting a preplanned correlative analysis of a phase II clinical trial in patients with small bowel adenocarcinoma (SBA). The cytolytic capacity of circulating immune cells in cancer patients using a novel ex vivo cytotoxicity assay is evaluated, and the utility of circulating biomarkers is investigated to predict and monitor the treatment effect of anti‐PD‐1. Baseline expression of Bim and NKG7 and upregulation of CX3CR1 in circulating T cells are associated with the clinical benefit of anti‐PD‐1 in patients with SBA. Overall, these findings suggest that the frequency and cytolytic capacity of circulating, effector immune cells may differentiate clinical response to ICIs, providing a strong rationale to support immune monitoring using patient peripheral blood.
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