Endocrine Abstracts

Background: Recently, immune checkpoint inhibitors (ICI) have been applied for the anaplastic thyroid cancer, and the need is increasing to optimize this treatment. The aim of this study is to investigate whether low dose radiotherapy can enhance the therapeutic efficacy of immune checkpoint inhibitor in a mouse anaplastic thyroid cancer model.

Methods: Mouse anaplastic thyroid cancer cell line TBP-3743 was implanted subcutaneously in C57BL/6 mouse. Mice were randomized into 5 groups after tumor reaching to 200 mm³ : control group (Con), anti-PD-L1 treated group (PDL1), conventional dose radiotherapy group (CRT), combination of anti-PD-L1 with conventional dose radiotherapy group (PDL1+CRT), combine anti-PD-L1 with low dose radiotherapy group (PDL1+LRT). Mice were treated with two times of anti-PD-L1 antibody at day 1, day 4 and with one fraction of radiation at day 1 (Conventional dose: 8 Gy, Low dose: 0.8 Gy). After that, tumor size and survival were evaluated. Tumors were analyzed for CD8, Granzyme B at day 7. Tumors were analyzed for CD8, granzyme B using immunohistochemistry and for CD45+ cells using flow cytometry, and for the mRNA expression level of IL-12 using RT-qPCR at day 7.

Result: Combination therapy increased mouse survival and reduced tumor volume compare to monotherapy (Median survival Con, PDL1, CRT, PDL1+CRT, PDL1+LRT; 15d, 26d, 26d, 38d, 37d respectively, P < 0.0001). Leukocytes increased in PDL1, PDL1+CRT, PDL1+LRT groups in terms of CD45 expression after flow cytometry analysis. Cytotoxic CD8 T and NK cell significantly increased in combination therapy group (PDL1+CRT, PDL1+LRT) than PDL1 or CRT group (P = 0.016). IL-12 mRNA level in tumor from PD-L1 and combined therapy group were significantly increased compared to the CRT group.

Conclusion: Low dose radiotherapy appears to therapeutic efficacy of anti PD-L1 antibody comparable to the conventional dose radiotherapy in a mouse anaplastic thyroid cancer model.