Localized ablative immunotherapy drives de novo CD8⁺ T-cell responses to poorly immunogenic tumors.

ABSTRACT:

Background

Localized ablative immunotherapies hold great promise in stimulating antitumor immunity to treat metastatic and poorly immunogenic tumors. Tumor ablation is well known to release tumor antigens and danger-associated molecular patterns to stimulate T-cell immunity, but its immune stimulating effect is limited, particularly against metastatic tumors.

Methods

In this study, we combined photothermal therapy with a potent immune stimulant, N-dihydrogalactochitosan, to create a local ablative immunotherapy which we refer to as laser immunotherapy (LIT). Mice bearing B16-F10 tumors were treated with LIT when the tumors reached 0.5 cm³ and were monitored for survival, T-cell activation, and the ability to resist tumor rechallenge.

Results

We found that LIT stimulated a stronger and more consistent antitumor T-cell response to the immunologically 'cold' B16-F10 melanoma tumors and conferred a long-term antitumor memory on tumor rechallenge. Furthermore, we discovered that LIT generated de novo CD8⁺ T-cell responses that strongly correlated with animal survival and tumor rejection.

Conclusion

In summary, our findings demonstrate that LIT enhances the activation of T cells and drives de novo antitumor T-cell responses. The data presented herein suggests that localized ablative immunotherapies have great potential to synergize with immune checkpoint therapies to enhance its efficacy, resulting in improved antitumor immunity.

SUBMITTER: Hoover AR 

PROVIDER: S-EPMC9577935 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature