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

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http://hdl.handle.net/10138/299674

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Taipale , K , Tähtinen , S , Havunen , R , Koski , A , Liikanen , I , Pakarinen , P , Koivisto-Korander , R , Kankainen , M , Joensuu , T , Kanerva , A & Hemminki , A 2018 , ' Interleukin 8 activity influences the efficacy of adenoviral oncolytic immunotherapy in cancer patients ' , Oncotarget , vol. 9 , no. 5 , pp. 6320-6335 . https://doi.org/10.18632/oncotarget.23967

Title: Interleukin 8 activity influences the efficacy of adenoviral oncolytic immunotherapy in cancer patients
Author: Taipale, Kristian; Tähtinen, Siri; Havunen, Riikka; Koski, Anniina; Liikanen, Ilkka; Pakarinen, Päivi; Koivisto-Korander, Riitta; Kankainen, Matti; Joensuu, Timo; Kanerva, Anna; Hemminki, Akseli
Contributor: University of Helsinki, Akseli Eetu Hemminki / Principal Investigator
University of Helsinki, Akseli Eetu Hemminki / Principal Investigator
University of Helsinki, Akseli Eetu Hemminki / Principal Investigator
University of Helsinki, HUS Neurocenter
University of Helsinki, Akseli Eetu Hemminki / Principal Investigator
University of Helsinki, HUS Gynecology and Obstetrics
University of Helsinki, HUS Gynecology and Obstetrics
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Docrates Cancer Center, Helsinki
University of Helsinki, Akseli Eetu Hemminki / Principal Investigator
University of Helsinki, Department of Oncology
Date: 2018
Language: eng
Number of pages: 16
Belongs to series: Oncotarget
ISSN: 1949-2553
URI: http://hdl.handle.net/10138/299674
Abstract: 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. © Taipale et al.
Subject: chemokine receptor CXCR1
chemokine receptor CXCR2
interleukin 8
neutralizing antibody
oncolytic adenovirus, Article
cancer immunotherapy
cancer patient
cancer prognosis
cancer survival
CD3+ T lymphocyte
cell culture
cohort analysis
cytokine production
disease association
drug efficacy
ex vivo study
human
human cell
human tissue
major clinical study
malignant neoplasm
microarray analysis
neutrophil lymphocyte ratio
oncolytic virotherapy
ovary tumor
overall survival
protein blood level
treatment response
tumor associated leukocyte
3122 Cancers
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