Evaluation of the abscopal-like effect of radioimmunotherapy on sentinel lymph nodes in H22 hepatocellular carcinoma via dynamic lymphography.

Background: The synergistic suppressive effects of the radioimmunotherapy-induced abscopal effect on distant non-irradiated tumors have recently emerged as a research hotspot. However, studies on its specific regulatory role in adjacent sentinel lymph nodes (SLNs) remain limited. The deep location and small size of SLNs hinder the monitoring of treatment-related changes, underscoring the need for lymphography-based approaches. In this study, we aimed to evaluate the abscopal-like effect of radioimmunotherapy on SLNs in an H22 hepatocellular carcinoma mouse model via dynamic lymphography.

Methods: H22 murine hepatocarcinoma cells were transplanted into the right hind foot sole of C57BL/6 mice. Fourteen days post-inoculation, mice with SLNs were selected and divided into six groups: control, isotype control Ig, anti-PD-1 alone, irradiation (IR) alone, irradiation + isotype control Ig, and IR + anti-PD-1. The volume and weights of tumors and non-irradiated SLNs were measured. The SLNs were imaged with ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) dynamic lymphography at 14, 21, and 28 days post-inoculation. CD8 immunohistochemistry assays were performed to assess CD8⁺ T cell infiltration.

Results: In this mouse model, the IR + anti-PD-1 combination treatment exerted a marked suppressive effect on the growth of both irradiated tumors and non-irradiated SLNs, demonstrating a robust enhancement of the abscopal-like effect compared with the monotherapy groups. Mechanistic investigations demonstrated elevated CD8⁺ T cell infiltration in non-irradiated SLNs, suggesting that enhanced systemic anti-tumor immunity mediated the effect. Dynamic ¹⁸F-FDG PET lymphography enabled clear visualization of SLNs as early as 30 s post-injection, with sustained imaging clarity for over 30 min. This method also demonstrated decreased radioactive accumulation in irradiated tumors and non-irradiated SLNs, confirming an enhanced abscopal-like effect with the IR and anti-PD-1 combination approach.

Conclusions: Our data demonstrate that the regression of SLNs adjacent to the irradiation field, mediated by the abscopal-like effect of radioimmunotherapy, can be sensitively and effectively tracked via dynamic ¹⁸F-FDG lymphography. Furthermore, our findings provide an effective and straightforward lymphographic approach with substantial translational potential for assessing the efficacy of the radioimmunotherapeutic abscopal-like effect against SLNs.