Identification of a novel peptide targeting TIGIT to evaluate immunomodulation of 125I seed brachytherapy in HCC by near-infrared fluorescence

Peng Zeng; Duo Shen; Wenbin Shu; Shudan Min; Min Shu; Xijuan Yao; Yong Wang; Rong Chen

doi:10.3389/fonc.2023.1143266

Identification of a novel peptide targeting TIGIT to evaluate immunomodulation of ¹²⁵I seed brachytherapy in HCC by near-infrared fluorescence

Front Oncol. 2023 Apr 14:13:1143266. doi: 10.3389/fonc.2023.1143266. eCollection 2023.

Authors

Peng Zeng¹, Duo Shen², Wenbin Shu³, Shudan Min⁴, Min Shu⁴, Xijuan Yao⁵, Yong Wang⁵, Rong Chen¹

Affiliations

¹ Department of Oncology, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu, China.
² Department of Gastroenterology, The Second People's Hospital of Changzhou, Nanjing Medical University, Changzhou, Jiangsu, China.
³ Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
⁴ Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu, China.
⁵ Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu, China.

Abstract

Introduction: Hepatocellular carcinoma (HCC) has very poor prognosis due to its immunosuppressive properties. An effective measure to regulate tumor immunity is brachytherapy, which uses ¹²⁵I seeds planted into tumor. T cell immune receptors with immunoglobulin and ITIM domains (TIGIT) is highly expressed in HCC. The TIGIT-targeted probe is expected to be an effective tool for indicating immunomodulation of ¹²⁵I seed brachytherapy in HCC. In this study, We constructed a novel peptide targeting TIGIT to evaluate the immune regulation of ¹²⁵I seed brachytherapy for HCC by near-infrared fluorescence (NIRF).

Methods: Expression of TIGIT by immunofluorescence (IF) and flow cytometry (FCM) in different part and different differentiated human liver cancer tissues was verified. An optical fluorescence probe (Po-12) containing a NIRF dye and TIGIT peptide was synthesized for evaluating the modulatory effect of ¹²⁵I seed brachytherapy. Lymphocytes uptake by Po-12 were detected by FCM and confocal microscopy. The distribution and accumulation of Po-12 in vivo were explored by NIRF imaging in subcutaneous and orthotopic tumors. IHC and IF staining were used to verify the expression of TIGIT in the tumors.

Results: TIGIT was highly expressed in HCC and increased with tumor differentiation. The dye-labeled peptide (Po-12) retained a stable binding affinity for the TIGIT protein in vitro. Accumulation of fluorescence intensity (FI) increased with time extended in subcutaneous H22 tumors, and the optimal point is 1 h. TIGIT was highly expressed on lymphocytes infiltrated in tumors and could be suppressed by ¹²⁵I seed brachytherapy. Accumulation of Po-12-Cy5 was increased in tumor-bearing groups while declined in 125I radiation group.

Keywords: 125I seed brachytherapy; NIRF; TIGIT; hepatocellular carcinoma; peptide.

Grants and funding

The study was supported by Jiangsu Provincial Special Program of Medical Science (BE2019750), National Natural Science Foundation of China (81827805), National Key Research and Development Program (2018YFA0704100, 2018YFA0704104), Science Fund for Creative Research Groups of the National Natural Science Foundation of China (61821002) and Interventional radiology scientific research special fund project of Jiangsu medical association (SYH-3201140-0025(2021020))for their financial supports.