Combination of radiation and interleukin 12 eradicates large orthotopic hepatocellular carcinoma through immunomodulation of tumor microenvironment

Oncoimmunology
Chia-Jen WuMi-Hua Tao

Abstract

Immunotherapies have shown promising results in certain cancer patients. For hepatocellular carcinoma (HCC), the multiplicity of an immunotolerant microenvironment within both the tumor, and the liver per se may limit the efficacy of cancer immunotherapies. Since radiation induces immunogenic cell death and inflammatory reactions within the tumor microenvironment, we hypothesized that a combination therapy of radiation and lasting local immunostimulating agents, achieved by intratumoral injection of an adenoviral vector encoding interleukin 12, may reverse the immunotolerant microenvironment within a well-established orthotopic HCC toward a state favorable for inducing antitumor immunities. Our data showed that radiation and IL-12 combination therapy (RT/IL-12) led to dramatic tumor regression in animals bearing large subcutaneous or orthotopic HCC, induced systemic effect against distant tumor, and significantly prolonged survival. Radiation monotherapy induced tumor regression at early times but afterwards most tumors regained exponential growth, while IL-12 monotherapy only delayed tumor growth. Mechanistic studies revealed that RT/IL-12 increased expression of MHC class II and co-stimulatory molecules CD40 and CD86 on tumor...Continue Reading

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Citations

Oct 28, 2019·Oncoimmunology·Jenny SprootenAbhishek D Garg
Mar 13, 2020·International Journal of Cancer. Journal International Du Cancer·Sarun JuengpanichXiujun Cai
Sep 11, 2019·Journal of Experimental & Clinical Cancer Research : CR·Yaojie FuHong Shen
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May 25, 2021·Frontiers in Immunology·Isabella LurjeLinda Hammerich
Jan 14, 2022·Cancer Immunology, Immunotherapy : CII·Emily M ChengAlexander L Rakhmilevich

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Methods Mentioned

BETA
flow cytometry
PMA

Software Mentioned

FlowJo

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