Page 77 - Read Online

Miliotis et al. J Cancer Metastasis Treat 2020;6:13 I http://dx.doi.org/10.20517/2394-4722.2020.12 Page 11 of 15

oncogenic activation of intrinsic signaling pathways, increased sensitivity to PD-L1 inducing signals from
the tumor microenvironment, and post-transcriptional control mechanisms. Overall, the regulation of
PD-L1 expression in EBVaGC is poorly understood and further studies are necessary to explain how EBV
and host factors contribute to it. Insight into the important genetic and epigenetic factors that control
PD-L1 expression in EBVaGC and other cancers could reveal new biomarkers for positive response to
immunotherapy, as well as novel therapeutic targets.

DECLARATIONS
Acknowledgments
We especially appreciate Dr. Maria Mavrikaki, Allison Baker, Tanvi Saxena, and Jason Nomburg for their
comments on this manuscript.

Authors’ contributions
Wrote the manuscript: Miliotis CN, Slack FJ

Availability of data and materials
Not applicable.

Financial support and sponsorship
Slack FJ acknowledges the NCI Outstanding Investigator Award (R35CA232105) and the support of the
Ludwig Institute at Harvard and the V Foundation.

Conflicts of interest
Slack FJ discloses financial interests and SAB roles with Mira DX and MiRNA Therapeutics. The other
author declares no competing financial interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2020.

REFERENCES
1. Rawla P, Barsouk A. Epidemiology of gastric cancer: global trends, risk factors and prevention. Prz Gastroenterol 2019;14:26-38.
2. Street W. Cancer facts & figures 2019. 1930:76.
3. Zali H, Rezaei-Tavirani M, Azodi M. Gastric cancer: prevention, risk factors and treatment. Gastroenterol Hepatol Bed Bench
2011;4:175-85.
4. Cancer Genome Atlas Research Network. Comprehensive molecular characterization of gastric adenocarcinoma. Nature 2014;513:202-9.
5. Angell HK, Lee J, Kim KM, Kim K, Kim ST, et al. PD-L1 and immune infiltrates are differentially expressed in distinct subgroups of
gastric cancer. Oncoimmunology 2019;8:e1544442.
6. Kim ST, Cristescu R, Bass AJ, Kim KM, Odegaard JI, et al. Comprehensive molecular characterization of clinical responses to PD-1
inhibition in metastatic gastric cancer. Nat Med 2018;24:1449-58.
7. Rickinson A. Epstein-Barr virus. Virus Res 2001;82:109-13.
8. Balfour HH Jr, Dunmire SK, Hogquist KA. Infectious mononucleosis. Clin Transl Immunol 2015;4:e33.
9. Epstein M, Achong B, Barr Y. Virus particles in cultured lymphoblasts from Burkitt’s lymphoma. Lancet 1964;283:702-3.
10. Dalldorf G, Linsell CA, Barnhart FE, Martyn R. An epidemiologic approach to the lymphomas of African children and Burkitt’s sacroma
of the jaws. Perspect Biol Med 1964;7:435-49.
11. Hsu JL, Glaser SL. Epstein-Barr virus-associated malignancies: epidemiologic patterns and etiologic implications. Crit Rev Oncol