Prognostic Value of Pd-L1 Expression Combined with Hypoxia-Associated Immunosuppression in Hepatocellular Carcinoma

Abstract

Background: Hypoxia and immunosuppression are two properties of cancer. This study intends to establish the potential relationship between these two hallmarks in hepatocellular carcinoma (HCC). Materials & methods: A bioinformatics analysis of data obtained from the Cancer Genome Atlas and a retrospective single-center analysis based on a tissue microarray were utilized in this study. Results: We identified a hypoxia-high subtype of patients with immunosuppressive HCC which represented a poor prognosis in the Cancer Genome Atlas cohort. Immunohistochemical analysis of the tissue microarray showed that tumor PD-L1 expression was positively linked to HIF-1α expression, pro-tumor immunocyte infiltration and poor survival in HCC patients. Conclusion: This study provides evidence supporting the correlation between hypoxic signals and immunosuppression in HCC; the combined use of them might improve survival prediction and act as a potential predictor for PD-1/PD-L1 therapy.

Keywords:

• CD68⁺ macrophages
• CD8⁺ T cells
• HCC
• HIF-1α
• PD-L1
• prognosis

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/bmm-2021-1051

Author contributions

Y Qian: conceptualization, data curation, formal analysis, funding acquisition, investigation, visualization, writing – original draft. H Su: data curation, validation, investigation. Y Ge: investigation, validation. K Lei: investigation, visualization. Y Li: methodology, validation. H Fan: conceptualization, funding acquisition, project administration, resources, supervision, writing – review and editing.

Acknowledgements

The authors are thankful to Z Zhang from the First Affiliated Hospital of Nanjing Medical University, Nanjing, China for helping us collecting HCC cases and providing us with the tissue microarray.

Financial & competing interests disclosure

This work was supported by the National Natural Science Foundation of China under Grant (81972664, 81702906 and 81672414). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

This study was approved by the Research Ethics Committee of the First Affiliated Hospital of Nanjing Medical University, and carried out according to the ethical guidelines of the Helsinki Declaration. Informed consent was obtained from all the patients.