A Paradigm of Cancer Immunotherapy Based on 2-[18F]FDG and Anti-PD-L1 mAb Combination to Enhance the Antitumor Effect.

Abstract

PURPOSE:

Efforts have been devoted to select eligible candidates for PD-1/PD-L1 immune checkpoint blocker (ICB) immunotherapy. Here, we have a serendipitous finding of positron emission tomography (PET) imaging tracer 2-[18F]FDG as a potential immunomodulator. Therefore, we hypothesize that 2-[18F]FDG could induce PD-L1 expression change and create an immune-favorable microenvironment for tumor immunotherapy.

EXPERIMENTAL DESIGN:

We designed a series of assays to verify PD-L1 upregulation, and tested immunotherapy regimens based on 2-[18F]FDG and anti-PD-L1 mAb, as monotherapy and in combination, in fully immunocompetent mice of MC38 and CT26 models. PD-L1 expression and tumor microenvironment (TME) changes were analyzed by Western blot, transcriptomics study, and flow-cytometric analysis.

RESULTS:

PD-L1 was upregulated in a time- and dose-dependent manner after being induced by 2-[18F]FDG. The activation of NF-κB/IRF3 pathway and STAT1/3-IRF1 pathway play crucial parts in modulating PD-L1 expression after DNA damage and repair. Improved αPD-L1 mAb utilization rate and significant tumor growth delay were observed when the personalized therapeutic alliance of 2-[18F]FDG stimulation and ICB was used. In addition, combination of 2-[18F]FDG with αPD-L1 mAb could reprogram a TME from "cold" to "hot," to make low immunoactivity tumors sensitive to ICB therapy.

CONCLUSIONS:

In summary, this promising paradigm has the potential to expand the traditional tumor theranostics. 2-[18F]FDG-based ICB immunotherapy is highly significant in enhancing antitumor effect. A research of 2-[18F]FDG-based ICB immunotherapy has been proposed to enhance the antitumor effect.

• Authors: Xuejun Wen, Changrong Shi, Xinying Zeng, Liang Zhao, Lanlin Yao, Zhida Liu, Lixia Feng, Deliang Zhang, Jinxiong Huang, Yesen Li, Qin Lin, Haojun Chen, Rongqiang Zhuang, Xiaoyuan Chen, Xianzhong Zhang, Zhide Guo
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 28 Issue 13 Pg. 2923-2937 (07 01 2022) ISSN: 1557-3265 [Electronic] United States
• PMID: 35320358 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2022 American Association for Cancer Research.

Chemical References

• B7-H1 Antigen
• Immunologic Factors
• Fluorodeoxyglucose F18

Topics

• Animals
• B7-H1 Antigen
• Cell Line, Tumor
• Fluorodeoxyglucose F18
• Immunologic Factors (pharmacology)
• Immunotherapy (methods)
• Mice
• Neoplasms (diagnostic imaging, therapy)
• Positron-Emission Tomography
• Tumor Microenvironment