Research Papers:

Interleukin 8 activity influences the efficacy of adenoviral oncolytic immunotherapy in cancer patients

Kristian Taipale, Siri Tähtinen Tähtinen, Riikka Havunen, Anniina Koski, Ilkka Liikanen, Päivi Pakarinen Pakarinen, Riitta Koivisto-Korander, Matti Kankainen, Timo Joensuu, Anna Kanerva and Akseli Hemminki _

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2018; 9:6320-6335. https://doi.org/10.18632/oncotarget.23967

Metrics: PDF 1797 views  |   HTML 2744 views  |   ?  


Kristian Taipale1, Siri Tähtinen1, Riikka Havunen1, Anniina Koski1,2, Ilkka Liikanen1, Päivi Pakarinen3, Riitta Koivisto-Korander3, Matti Kankainen4, Timo Joensuu5, Anna Kanerva1,3 and Akseli Hemminki1,5,6,7

1Cancer Gene Therapy Group, University of Helsinki, Faculty of Medicine, Helsinki, Finland

2Department of Neurosurgery, HUCH, Helsinki, Finland

3Department of Obstetrics and Gynecology, HUCH, Helsinki, Finland

4Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland

5Docrates Cancer Center, Helsinki, Finland

6TILT Biotherapeutics Ltd., Helsinki, Finland

7Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland

Correspondence to:

Akseli Hemminki, email: [email protected]

Keywords: oncolytic adenovirus; neutrophils; anti-tumor immunity; cytokines; immunomodulation

Received: March 29, 2017    Accepted: December 12, 2017    Published: January 05, 2018


After the landmark approval of T-VEC, oncolytic viruses are finding their way to the clinics. However, response rates have still room for improvement, and unfortunately there are currently no available markers to predict responses for oncolytic immunotherapy. Interleukin 8 (IL-8) production is upregulated in many cancers and it also connects to several pathways that have been shown to impair the efficacy of adenoviral immunotherapy. We studied the role of IL-8 in 103 cancer patients treated with oncolytic adenoviruses. We found high baseline serum IL-8 concentration to be independently associated with poor prognosis (p<0.001). Further, normal baseline IL-8 was associated with improved prognostic potential of calculation of the neutrophil-to-lymphocyte ratio (p<0.001). Interestingly, a decrease in IL-8 concentration after treatment with oncolytic adenovirus predicted better overall survival (p<0.001) and higher response rate, although this difference was not significant (p=0.066). We studied the combination of adenovirus and IL-8 neutralizing antibody ex vivo in single cell suspensions and in co-cultures of tumor-associated CD15+ neutrophils and CD3+ tumor-infiltrating lymphocytes derived from fresh patient tumor samples. These results indicate a role for IL-8 as a biomarker in oncolytic virotherapy, but additionally provide a rationale for targeting IL-8 to improve treatment efficacy. In conclusion, curtailing the activity of IL-8 systemically or locally in the tumor microenvironment could improve anti-tumor immune responses resulting in enhanced efficacy of adenoviral immunotherapy of cancer.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 23967