Cryoablation Does Not Significantly Contribute to Systemic Effector Immune Responses in a Poorly Immunogenic B16F10 Melanoma Model.
Details
Serval ID
serval:BIB_4F4C3A79A0FC
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Cryoablation Does Not Significantly Contribute to Systemic Effector Immune Responses in a Poorly Immunogenic B16F10 Melanoma Model.
Journal
Clinical cancer research
ISSN
1557-3265 (Electronic)
ISSN-L
1078-0432
Publication state
Published
Issued date
13/09/2024
Peer-reviewed
Oui
Volume
30
Number
18
Pages
4190-4200
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Abstract
Cryoablation is a minimally invasive procedure implemented to destroy solid tumors. It also results in the release of tumor antigens into the systemic circulation. Preclinical studies using immunogenic tumor models have shown that cryoablation evokes antitumor immune responses. The mechanisms by which cryoablation impacts immune responses in poorly immunogenic tumors have not been sufficiently explored.
We used a bilateral B16F10 melanoma model devoid of strong immunogenic antigens. Cryoablation-induced effector immune responses were investigated, also in combination with a peritumoral STING agonist and systemic anti-PD-1. Selective immune cell depletion, T-cell migration arrest, in vivo T-cell transplantation, and cryoablation versus surgical removal techniques were used to determine the contribution of cryoablation and immunotherapies to systemic antitumor effector immune responses.
Treatment of a tumor with cryoablation + STING agonist + anti-PD-1 resulted in the rejection of unablated, contralateral tumors. Depletion studies demonstrated that 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-PD-1 versus surgery + STING agonist + anti-PD-1 in the bilateral tumor model showed no difference in the rejection of contralateral tumors.
Cryoablation does not significantly contribute to systemic antitumor effector immune responses in a B16F10 melanoma model. Cryoablation primarily performs tumor debulking, and immunotherapy functions independently of cryoablation in eliciting antitumor effector immune responses.
We used a bilateral B16F10 melanoma model devoid of strong immunogenic antigens. Cryoablation-induced effector immune responses were investigated, also in combination with a peritumoral STING agonist and systemic anti-PD-1. Selective immune cell depletion, T-cell migration arrest, in vivo T-cell transplantation, and cryoablation versus surgical removal techniques were used to determine the contribution of cryoablation and immunotherapies to systemic antitumor effector immune responses.
Treatment of a tumor with cryoablation + STING agonist + anti-PD-1 resulted in the rejection of unablated, contralateral tumors. Depletion studies demonstrated that 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-PD-1 versus surgery + STING agonist + anti-PD-1 in the bilateral tumor model showed no difference in the rejection of contralateral tumors.
Cryoablation does not significantly contribute to systemic antitumor effector immune responses in a B16F10 melanoma model. Cryoablation primarily performs tumor debulking, and immunotherapy functions independently of cryoablation in eliciting antitumor effector immune responses.
Keywords
Animals, Cryosurgery/methods, Mice, Melanoma, Experimental/immunology, Melanoma, Experimental/pathology, Melanoma, Experimental/surgery, CD8-Positive T-Lymphocytes/immunology, Disease Models, Animal, Cell Line, Tumor, Female, Immunotherapy/methods, Mice, Inbred C57BL
Pubmed
Web of science
Create date
24/07/2024 9:10
Last modification date
29/10/2024 7:21