Detection and characterization of cryoimmunologic response induced by ultrasound-guided cryoablation on early breast cancer: evaluation of circulating markers
Author Block: F. Galati, M. Pasculli, C. Napoletano, V. Rizzo, R. Maroncelli, F. Cicciarelli, M. Nuti, C. Catalano, F. Pediconi; Rome/IT
Purpose: Cryoablation is a minimally-invasive procedure that uses cooling to induce necrosis of the targeted tissue. All other minimally invasive techniques use hyperthermia, which melts cell membranes and causes protein denaturation. In contrast, cryoablation leaves tumor proteins and tumor-associated antigens intact, with the potential to stimulate an anti-tumor immune response. Thus, the purpose of this prospective pilot study was to characterize the immune response induced by tumor cryoablation in blood samples from early breast cancer (BC) patients.
Methods or Background: We enrolled patients with early-stage BC, scheduled for breast surgery, not eligible for neo-adjuvant therapy, and with a cryo-feasible cancer location. Blood samples to assess immune response were taken before (T0) and one week after cryoablation (T1), and before (T2) and one week after (T3) surgery. Analysis of T cell subsets (CD3, CD8, CD4, CD137, and Tregs) and the inflammatory/damage molecule HMGB1 were performed by flow cytometry/ELISA. Circulating cytokines were also analyzed using the Luminex analysis.
Results or Findings: From July 2022 to January 2023, ten patients underwent cryoablation. Analysis of circulating markers of cryo-immunological response revealed a progressive release of HGBM1 after cryoablation (T0-T1, p=0.04) until surgical resection of the primary tumor (T0-T3, p=0.02). Cryoablation followed by surgery also induced a significant decrease in CD137 T cell subsets (total and CD4; p<0.01), and IL4 (T0-T3, p<0.05). Finally, a significant decrease in proliferative Treg cell subsets (Ki67+Tregs; p<0.05) was observed.
Conclusion: In our pilot study, cryoablation induced the release of HMGB1, which acts to activate the primary phases of the immune response, and the decrease of the immunosuppressive Treg subset and the pro-tumoral cytokine IL-4, probably released by CD4CD137 T cells.
Limitations: Although the limited number of patients, cryoablation was a valuable method to enhance the anti-tumor response.
Funding for this study: The study has received funding from the Seed Grant funding programme of the European Society of Radiology (ESR) in collaboration with the European Institute for Biomedical Imaging Research (EIBIR) kindly supported by an unrestricted, non-exclusive grant from GE Healthcare.
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: The study obtained the approval of the Institutional Review Board of “Sapienza” University of Rome (Ref.6528, approved 24.11.2021).