Radiotherapy in combination with CD47 blockade elicits a macrophage-mediated abscopal effect.
Radiotherapy in combination with CD47 blockade elicits a macrophage-mediated abscopal effect.
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DOI：
10.1038/s43018-022-00456-0
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发表时间：
2022-11
期刊：
影响因子：
22.7
通讯作者：
Sage, Julien
中科院分区：
文献类型：
--
作者：
Nishiga, Yoko;Drainas, Alexandros P.;Baron, Maya;Bhattacharya, Debadrita;Barkal, Amira A.;Ahrari, Yasaman;Mancusi, Rebecca;Ross, Jason B.;Takahashi, Nobuyuki;Thomas, Anish;Diehn, Maximilian;Weissman, Irving L.;Graves, Edward E.;Sage, Julien
放射治疗是癌症治疗的主要手段，但并不总是导致肿瘤完全消退。在这里，我们将联合收割机与阻断小细胞肺癌（SCLC）（一种高转移性肺癌）中的“不要吃我”细胞表面分子CD 47相结合。在SCLC临床前模型中，CD47阻断剂可有效增强放疗的局部抗肿瘤作用。值得注意的是，CD47阻断还刺激脱靶“远位”效应，抑制接受辐射的小鼠中的未辐射的SCLC肿瘤。这些远位效应不依赖于T细胞，但需要巨噬细胞响应于辐射产生的炎症信号而迁移到未辐射的肿瘤部位，并通过CD47阻断局部激活以吞噬癌细胞。在用辐射和CD47阻断治疗的其他癌症模型中观察到类似的远位抗肿瘤作用。放疗和CD47阻断后抗肿瘤巨噬细胞的全身活化在患有转移性疾病的癌症患者中可能特别重要。Nishiga及其同事显示了放疗和CD 47阻断相结合的治疗效果，这还引起了由巨噬细胞迁移到未照射的肿瘤部位并吞噬癌细胞介导的远隔效应。
Radiation therapy is a mainstay of cancer treatment but does not always lead to complete tumor regression. Here we combine radiotherapy with blockade of the ‘don’t-eat-me’ cell-surface molecule CD47 in small cell lung cancer (SCLC), a highly metastatic form of lung cancer. CD47 blockade potently enhances the local antitumor effects of radiotherapy in preclinical models of SCLC. Notably, CD47 blockade also stimulates off-target ‘abscopal’ effects inhibiting non-irradiated SCLC tumors in mice receiving radiation. These abscopal effects are independent of T cells but require macrophages that migrate into non-irradiated tumor sites in response to inflammatory signals produced by radiation and are locally activated by CD47 blockade to phagocytose cancer cells. Similar abscopal antitumor effects were observed in other cancer models treated with radiation and CD47 blockade. The systemic activation of antitumor macrophages following radiotherapy and CD47 blockade may be particularly important in patients with cancer who suffer from metastatic disease. Nishiga and colleagues show therapeutic efficacy for a combination of radiotherapy and CD47 blockade, which also elicits an abscopal effect mediated by macrophages migrating into non-irradiated tumor sites and phagocytosing cancer cells.
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DOI：
10.1158/1078-0432.ccr-09-0265
发表时间：
2009-09-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Dewan MZ;Galloway AE;Kawashima N;Dewyngaert JK;Babb JS;Formenti SC;Demaria S
通讯作者：
Demaria S
DOI：
10.1158/1078-0432.ccr-10-3420
发表时间：
2011-09-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Daldrup-Link HE;Golovko D;Ruffell B;Denardo DG;Castaneda R;Ansari C;Rao J;Tikhomirov GA;Wendland MF;Corot C;Coussens LM
通讯作者：
Coussens LM
影响因子：
6.2
作者：
Byers LA;Rudin CM
通讯作者：
Rudin CM
影响因子：
82.9
作者：
Formenti SC;Rudqvist NP;Golden E;Cooper B;Wennerberg E;Lhuillier C;Vanpouille-Box C;Friedman K;Ferrari de Andrade L;Wucherpfennig KW;Heguy A;Imai N;Gnjatic S;Emerson RO;Zhou XK;Zhang T;Chachoua A;Demaria S
通讯作者：
Demaria S
影响因子：
50.3
作者：
Gay CM;Stewart CA;Park EM;Diao L;Groves SM;Heeke S;Nabet BY;Fujimoto J;Solis LM;Lu W;Xi Y;Cardnell RJ;Wang Q;Fabbri G;Cargill KR;Vokes NI;Ramkumar K;Zhang B;Della Corte CM;Robson P;Swisher SG;Roth JA;Glisson BS;Shames DS;Wistuba II;Wang J;Quaranta V;Minna J;Heymach JV;Byers LA
通讯作者：
Byers LA