Effect of Interleukin-7 on Radiation-Induced Lymphopenia and Its Antitumor Effects in a Mouse Model

Abstract

Purpose: Local ionizing radiation (IR) can lead to systemic lymphocyte depletion, which is associated with poor survival outcomes in patients with cancer. Interleukin-7 (IL-7) plays an important role in lymphocyte homeostasis; however, its role in alleviating radiation-induced lymphopenia remains unclear. Hence, we established a radiation-induced lymphopenia animal model and evaluated the effect of exogenous IL-7 administration.

Methods: C3H/HeN mice underwent x-ray irradiation of 30 Gy in 10 fractions at the right hind limbs. Next, 10 mg/kg of IL-7 was injected subcutaneously, and the lymphocyte count in blood was measured. Murine hepatocellular carcinoma (HCa-1) cells were inoculated subcutaneously into the right thighs of tumor model mice, which underwent the same treatment.

Results: In the naïve mouse model, the decreased CD45+ cell count after irradiation gradually recovered to the initial level over 3 weeks in the IR group, whereas it markedly increased to 373% of the initial level in 1 week in the IR+IL-7 group. Similar trends were observed for the CD3+, CD8+, CD4+, regulatory T cells, and CD19+ B cell counts. Similar findings were observed in the tumor mouse model. CD8+ and CD4+ T cell infiltration in tumor specimens was higher in the IL-7 and IR+IL-7 groups than in the nontreated and IR groups. Tumor growth was significantly more suppressed in the IR+IL-7 group than in the IR group. The median survival time was significantly longer in the IR+IL-7 group (not reached) than in the IR (56 days; P = .0382), IL-7 (36 days; P = .0004), or nontreated groups (36 days; P < .0001).

Conclusions: Administration of exogenous IL-7 after IR not only restored lymphocyte counts but also enhanced the antitumor effect. Exogenous IL-7 can be beneficial in overcoming radiation-induced lymphopenia and in enhancing the treatment outcome in combination with radiation therapy, which needs validation through future clinical studies.