Cryoablation is a minimally invasive procedure implemented to destroy solid tumors. It also results in the release of tumor antigens into the systemic circulation. Pre-clinical studies employing immunogenic tumor models have shown that cryoablation evokes anti-tumor immune responses. How cryoablation impacts immune responses in poorly immunogenic tumors has not been sufficiently explored.
We employed bilateral, B16F10 melanoma model, devoid of strong immunogenic antigens. Cryoablation induced effector immune responses were investigated, also in combination with peritumoral STING agonist and systemic anti-PD1. Selective immune cell depletion, T-cell migration arrest, in vivo T-cell transplantation, and cryoablation vs surgical removal techniques were employed to determine the contribution of cryoablation and immunotherapies to systemic, anti-tumor, effector immune responses.
Treatment of a tumor with cryoablation + STING agonist + anti-PD1 resulted in the rejection of unablated, contralateral tumor. Depletion studies demonstrated that the tumor rejection is essentially dependent on CD8+ T-cells. T-cell arrest in the lymph nodes had no effect on the rejection process. Splenic CD8+ T-cells isolated from cryoablation treated mice with B16F10 melanoma, upon transplantation into melanoma bearing recipients did not impact the recipient's tumor growth. Finally, comparison of cryoablation + STING agonist + anti-PD1 vs surgery + STING agonist + anti-PD1 in bilateral tumor model showed no difference in the rejection of contralateral tumor.
Cryoablation does not significantly contribute to systemic, anti-tumor, effector immune responses in a B16F10 melanoma model. Cryoablation primarily performs tumor debulking, and immunotherapy functions independently of cryoablation in eliciting anti-tumor effector immune responses.