Radiation combines with immune checkpoint blockade to enhance T cell priming in a murine model of poorly immunogenic pancreatic cancer.
Radiation combines with immune checkpoint blockade to enhance T cell priming in a murine model of poorly immunogenic pancreatic cancer.
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DOI：
10.1098/rsob.210245
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发表时间：
2021-11
期刊：
影响因子：
5.8
通讯作者：
Dougan SK
中科院分区：
文献类型：
--
作者：
Stump CT;Roehle K;Manjarrez Orduno N;Dougan SK
几十年来，放射治疗一直是癌症治疗的支柱。辐射对抗肿瘤免疫应答的影响在研究中是可变的，并且在免疫原性差的肿瘤类型中尚未明确定义。在这里，我们采用了检查点阻断免疫治疗与立体定向体放射治疗的组合，并检查了对胰腺癌皮下和原位小鼠模型中肿瘤生长和免疫浸润的影响。尽管免疫检查点阻断和放射单独无效，但它们的组合在放射和非放射肿瘤中产生了适度的生长延迟，这与IFNγ ELISpot鉴定的CD8+ T细胞、CD4+ T细胞和肿瘤特异性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，并且这些T细胞的频率可以通过与免疫检查点阻断相结合来进一步增加。
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.
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DOI：
10.1158/1078-0432.ccr-16-0870
发表时间：
2017-01-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Kalbasi A;Komar C;Tooker GM;Liu M;Lee JW;Gladney WL;Ben-Josef E;Beatty GL
通讯作者：
Beatty GL
影响因子：
17.1
作者：
Krall JA;Reinhardt F;Mercury OA;Pattabiraman DR;Brooks MW;Dougan M;Lambert AW;Bierie B;Ploegh HL;Dougan SK;Weinberg RA
通讯作者：
Weinberg RA
影响因子：
3.8
作者：
Holyoake, Daniel L. P.;Ward, Elizabeth;Hawkins, Maria A.
通讯作者：
Hawkins, Maria A.
影响因子：
10.1
作者：
Dougan M;Ingram JR;Jeong HJ;Mosaheb MM;Bruck PT;Ali L;Pishesha N;Blomberg O;Tyler PM;Servos MM;Rashidian M;Nguyen QD;von Andrian UH;Ploegh HL;Dougan SK
通讯作者：
Dougan SK
影响因子：
28.2
作者：
Liudahl SM;Betts CB;Sivagnanam S;Morales-Oyarvide V;da Silva A;Yuan C;Hwang S;Grossblatt-Wait A;Leis KR;Larson W;Lavoie MB;Robinson P;Dias Costa A;Väyrynen SA;Clancy TE;Rubinson DA;Link J;Keith D;Horton W;Tempero MA;Vonderheide RH;Jaffee EM;Sheppard B;Goecks J;Sears RC;Park BS;Mori M;Nowak JA;Wolpin BM;Coussens LM
通讯作者：
Coussens LM