Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Department of Gastroenterology, Massachusetts General Hospital, Boston, MA 02215, USA.
Open Biol. 2021 Nov;11(11):210245. doi: 10.1098/rsob.210245. Epub 2021 Nov 17.
Radiation has been a pillar of cancer therapy for decades. The effects of radiation on the anti-tumour immune response are variable across studies and have not been explicitly defined in poorly immunogenic tumour types. Here, we employed combination checkpoint blockade immunotherapy with stereotactic body radiation therapy and examined the effect on tumour growth and immune infiltrates in subcutaneous and orthotopic mouse models of pancreatic cancer. Although immune checkpoint blockade and radiation were ineffective alone, their combination produced a modest growth delay in both irradiated and non-irradiated tumours that corresponded with significant increases in CD8+ T cells, CD4+ T cells and tumour-specific T cells as identified by IFNγ ELISpot. We conclude that radiation enhances priming of tumour-specific T cells in poorly immunogenic tumours and that the frequency of these T cells can be further increased by combination with immune checkpoint blockade.
几十年来，辐射一直是癌症治疗的基石。然而，辐射对抗肿瘤免疫反应的影响在不同的研究中存在差异，在免疫原性差的肿瘤类型中尚未明确界定。在这里，我们采用立体定向体部放射治疗联合联合检查点封锁免疫疗法，并在胰腺癌的皮下和原位小鼠模型中研究其对肿瘤生长和免疫浸润的影响。虽然免疫检查点阻断和辐射单独使用无效，但它们的联合治疗在辐照和未辐照肿瘤中均产生了适度的生长延迟，这与 CD8+T 细胞、CD4+T 细胞和 IFNγ ELISpot 鉴定的肿瘤特异性 T 细胞的显著增加相对应。我们得出结论，辐射增强了免疫原性差的肿瘤中肿瘤特异性 T 细胞的启动，并且通过与免疫检查点阻断联合使用，可以进一步增加这些 T 细胞的频率。
