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局部消融免疫疗法可诱导针对免疫原性弱肿瘤的新的 CD8 T 细胞反应。

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

机构信息

Stephenson School of Biomedical Engineering, The University of Oklahoma, Norman, Oklahoma, USA.

Department of Microbiology and Immunology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.

出版信息

J Immunother Cancer. 2022 Oct;10(10). doi: 10.1136/jitc-2022-004973.

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 cm 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.

摘要

背景

局部消融免疫疗法在刺激抗肿瘤免疫以治疗转移性和免疫原性差的肿瘤方面具有巨大的潜力。众所周知,肿瘤消融会释放肿瘤抗原和危险相关分子模式来刺激 T 细胞免疫,但它的免疫刺激作用有限,特别是对转移性肿瘤。

方法

在这项研究中,我们将光热疗法与一种有效的免疫刺激剂 N-二氢半乳糖壳聚糖结合,创建了一种局部消融免疫疗法,我们称之为激光免疫疗法(LIT)。当肿瘤达到 0.5 厘米时,携带 B16-F10 肿瘤的小鼠接受 LIT 治疗,并监测其生存、T 细胞激活以及抵抗肿瘤再挑战的能力。

结果

我们发现 LIT 刺激了对免疫“冷”B16-F10 黑色素瘤肿瘤更强、更一致的抗肿瘤 T 细胞反应,并赋予了肿瘤再挑战的长期抗肿瘤记忆。此外,我们发现 LIT 产生了新的 CD8 T 细胞反应,与动物的生存和肿瘤排斥强烈相关。

结论

总之,我们的研究结果表明,LIT 增强了 T 细胞的激活,并驱动了新的抗肿瘤 T 细胞反应。本文提供的数据表明,局部消融免疫疗法具有与免疫检查点疗法协同增效的巨大潜力,从而增强其疗效,提高抗肿瘤免疫能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f8e/9577935/c0e5cf0fd096/jitc-2022-004973f01.jpg

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