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Theranostics 2024; 14(2):699-713. doi:10.7150/thno.90709 This issue Cite

Research Paper

Annotation of CD8+ T-cell function via ICAM-1 imaging identifies FAK inhibition as an adjuvant to augment the antitumor immunity of radiotherapy

Ting Zhang1#, Yining Zhang1#, Yang Zhao1, Rui Song1, Yanpu Wang1, Kui Li1, Haoyi Zhou1, Feng Wang2, Shixin Zhou3, Meixin Zhao4, Hua Zhu2, Weifang Zhang4✉, Zhi Yang2✉, Zhaofei Liu1,2,4,5,6✉

1. Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
2. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine, Peking University Cancer Hospital and Institute, Beijing 100142, China.
3. Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
4. Department of Nuclear Medicine, Peking University Third Hospital, Beijing 100191, China.
5. State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing 100191, China.
6. Peking University-Yunnan Baiyao International Medical Research Center, Beijing 100191, China.
#These authors contributed equally to this work.

✉ Corresponding authors: Zhaofei Liu, E-mail: liuzfedu.cn; Zhi Yang, Email: pekyzcom; Weifang Zhang, Email: tsy1997com.

Citation:
Zhang T, Zhang Y, Zhao Y, Song R, Wang Y, Li K, Zhou H, Wang F, Zhou S, Zhao M, Zhu H, Zhang W, Yang Z, Liu Z. Annotation of CD8+ T-cell function via ICAM-1 imaging identifies FAK inhibition as an adjuvant to augment the antitumor immunity of radiotherapy. Theranostics 2024; 14(2):699-713. doi:10.7150/thno.90709. https://www.thno.org/v14p0699.htm
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Abstract

Graphic abstract

Background: Radiotherapy (RT) may trigger systemic antitumor immunity, manifesting as regression of non-irradiated lesions (abscopal effect). Intracellular adhesion molecule-1 (ICAM-1) is a key molecule involved in the abscopal effect of RT. However, the specific function of ICAM-1 in CD8+ T cells during antitumor immune responses remains unclear. Herein, we investigated whether noninvasive imaging of ICAM-1 can be used to annotate CD8+ T-cell function, thereby better selecting combinational therapy to enhance the antitumor immunity induced by RT.

Methods: Using knockout mouse models, we investigated the role of ICAM-1 expressed on CD8+ T cells in the antitumor immunity of RT and conducted drug screening guided by ICAM-1-targeted noninvasive imaging.

Results: The systemic antitumor effect of RT relies on the expression of ICAM-1 on CD8+ T cells. ICAM-1 expression is essential for CD8+ T-cell activation, proliferation, and effector function. Noninvasive annotation of the proliferation and effector function of CD8+ T cells by ICAM-1-targeted imaging identified VS-6063, a focal adhesion kinase inhibitor, as a new adjuvant to augment systemic antitumor immunity of RT in an immunologically “cold” tumor model. Mechanistically, VS-6063 overcomes the physical barriers in tumors and promotes the migration and infiltration of CD8+ T cells primed by RT into distant tumors.

Conclusion: Our findings highlight that molecular imaging of ICAM-1 levels provides a dynamic readout of the proliferation and effector function of tumor-infiltrating CD8+ T cells, which facilitates the high-throughput exploitation of new combinational drugs to maximize the systemic antitumor effect of RT.

Keywords: molecular imaging, positron emission tomography, radiotherapy, ICAM-1, focal adhesion kinase

Citation styles

APA
Zhang, T., Zhang, Y., Zhao, Y., Song, R., Wang, Y., Li, K., Zhou, H., Wang, F., Zhou, S., Zhao, M., Zhu, H., Zhang, W., Yang, Z., Liu, Z. (2024). Annotation of CD8+ T-cell function via ICAM-1 imaging identifies FAK inhibition as an adjuvant to augment the antitumor immunity of radiotherapy. Theranostics, 14(2), 699-713. https://doi.org/10.7150/thno.90709.

ACS
Zhang, T.; Zhang, Y.; Zhao, Y.; Song, R.; Wang, Y.; Li, K.; Zhou, H.; Wang, F.; Zhou, S.; Zhao, M.; Zhu, H.; Zhang, W.; Yang, Z.; Liu, Z. Annotation of CD8+ T-cell function via ICAM-1 imaging identifies FAK inhibition as an adjuvant to augment the antitumor immunity of radiotherapy. Theranostics 2024, 14 (2), 699-713. DOI: 10.7150/thno.90709.

NLM
Zhang T, Zhang Y, Zhao Y, Song R, Wang Y, Li K, Zhou H, Wang F, Zhou S, Zhao M, Zhu H, Zhang W, Yang Z, Liu Z. Annotation of CD8+ T-cell function via ICAM-1 imaging identifies FAK inhibition as an adjuvant to augment the antitumor immunity of radiotherapy. Theranostics 2024; 14(2):699-713. doi:10.7150/thno.90709. https://www.thno.org/v14p0699.htm

CSE
Zhang T, Zhang Y, Zhao Y, Song R, Wang Y, Li K, Zhou H, Wang F, Zhou S, Zhao M, Zhu H, Zhang W, Yang Z, Liu Z. 2024. Annotation of CD8+ T-cell function via ICAM-1 imaging identifies FAK inhibition as an adjuvant to augment the antitumor immunity of radiotherapy. Theranostics. 14(2):699-713.

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