| First Author | Zhang T | Year | 2024 |
| Journal | Theranostics | Volume | 14 |
| Issue | 2 | Pages | 699-713 |
| PubMed ID | 38169608 | Mgi Jnum | J:344448 |
| Mgi Id | MGI:7572122 | Doi | 10.7150/thno.90709 |
| Citation | Zhang T, et al. (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 |
| abstractText | 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. |
