High Dose Local Photon Irradiation Is Crucial in Anti-CTLA-4 Antibody Therapy to Enhance the Abscopal Response in a Murine Pancreatic Carcinoma Model.
High Dose Local Photon Irradiation Is Crucial in Anti-CTLA-4 Antibody Therapy to Enhance the Abscopal Response in a Murine Pancreatic Carcinoma Model.
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DOI：
10.3390/cancers14092087
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发表时间：
2022-04-22
期刊：
影响因子：
5.2
通讯作者：
Koizumi, Masahiko
中科院分区：
文献类型：
--
作者：
Yamamoto, Junya;Takahashi, Yutaka;Minami, Kazumasa;Tamari, Keisuke;Katsuki, Shohei;Takenaka, Wataru;Tatekawa, Shotaro;Hayashi, Kazuhiko;Seo, Yuji;Isohashi, Fumiaki;Ogawa, Kazuhiko;Koizumi, Masahiko
关键词：
胰腺癌是一种对化疗和免疫治疗极具抗药性的肿瘤。以小鼠胰腺导管腺癌(PDAC)为模型，研究了光子束照射与抗CTLA-4抗体(C4)联合应用对局部和远处肿瘤(远端肿瘤)的抗肿瘤效应。单用C4治疗对PDAC无效。大剂量照射局部肿瘤后，肿瘤体积明显缩小，但未引起异常反应。相比之下，大剂量辐射和C4的联合治疗增强了异常反应，显著延长了总生存期。联合治疗可显著减少放疗后肿瘤组织中调节性T细胞的浸润，增加肿瘤组织中的细胞毒性T淋巴细胞。这些结果表明，大剂量光子束照射在C4治疗中起着重要作用，以增强PDAC的非局域反应。胰腺癌是一种对化疗和免疫治疗极具抗药性的肿瘤。采用小鼠胰腺导管腺癌(PDAC)模型，研究了光子束照射与抗CTLA-4抗体(C4)联合应用对胰腺癌局部和远处肿瘤(远端肿瘤)的抗肿瘤效应。将Pan02细胞接种于C57BL/6小鼠双侧双腿。低分割或单一分割的高剂量光子束被输送到一条腿上的肿瘤。经腹腔注射C4单一疗法。对PDAC无效。高剂量照射可使局部肿瘤明显缩小，但未引起异常反应。相比之下，低分割和单一分割的高剂量光子束照射与C4的联合治疗增强了对异位肿瘤的抗肿瘤效果，显著延长了总生存期。流式细胞仪分析显示，联合治疗显著降低了局部和远端肿瘤中调节性T细胞(Treg)的比例，而增加了细胞毒性T淋巴细胞。这些结果表明，无论放射治疗的分割程度如何，大剂量光子束照射在C4治疗中都能增强免疫微环境的异常反应，在治疗中起重要作用。
Pancreatic cancer is an extremely treatment-resistant neoplasm to chemotherapy and immunotherapy. The combination of photon beam irradiation and anti-CTLA-4 antibody (C4) for the anti-tumor effect enhancement at local and distant tumors (abscopal tumors) was investigated using a pancreatic ductal adenocarcinoma (PDAC) mouse model. Monotherapy with C4 was not effective for PDAC. The high dose irradiation to local tumors produced significant shrinkage of irradiated tumors but did not induce the abscopal responses. In contrast, the combination therapy of high dose radiation and C4 enhanced the abscopal responses with significantly prolonged overall survival. The combination therapy dramatically decreased the regulatory T cell infiltration while increasing the cytotoxic T lymphocytes in the irradiated and abscopal tumors. These results suggest that high dose photon beam irradiation plays an important role in C4 therapy to enhance the abscopal response in PDAC. Pancreatic cancer is an extremely treatment-resistant neoplasm to chemotherapy and immunotherapy. The combination of photon beam irradiation and anti-CTLA-4 antibody (C4) for the anti-tumor effect enhancement at local and distant tumors (abscopal tumors) was investigated using the pancreatic ductal adenocarcinoma (PDAC) mouse model. Pan02 cells were bilaterally inoculated to both legs of C57BL/6 mice. High dose photon beams in a hypofractionation or a single fraction were delivered to the tumors on one leg. Monotherapy with C4 via i.p. was not effective for PDAC. The high dose irradiation to the local tumors produced significant shrinkage of irradiated tumors but did not induce the abscopal responses. In contrast, the combination therapy of high dose photon beam irradiation in both hypofractionation and a single fraction with C4 enhanced the anti-tumor effect for abscopal tumors with significantly prolonged overall survival. The flow cytometric analysis revealed that the combination therapy dramatically decreased the regulatory T cell (Treg) proportion while increasing the cytotoxic T lymphocytes in both local and abscopal tumors. These results suggest that high dose photon beam irradiation plays an important role in C4 therapy to enhance the abscopal response with immune microenvironment changes in PDAC, regardless of the fractionation in radiation therapy.
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DOI：
10.1073/pnas.1720948115
发表时间：
2018-04-24
影响因子：
11.1
作者：
Peranzoni E;Lemoine J;Vimeux L;Feuillet V;Barrin S;Kantari-Mimoun C;Bercovici N;Guérin M;Biton J;Ouakrim H;Régnier F;Lupo A;Alifano M;Damotte D;Donnadieu E
通讯作者：
Donnadieu E
影响因子：
8.8
作者：
Ino Y;Yamazaki-Itoh R;Shimada K;Iwasaki M;Kosuge T;Kanai Y;Hiraoka N
通讯作者：
Hiraoka N
影响因子：
--
作者：
Diana A;Wang LM;D'Costa Z;Allen P;Azad A;Silva MA;Soonawalla Z;Liu S;McKenna WG;Muschel RJ;Fokas E
通讯作者：
Fokas E
影响因子：
7.2
作者：
Golden EB;Frances D;Pellicciotta I;Demaria S;Helen Barcellos-Hoff M;Formenti SC
通讯作者：
Formenti SC
影响因子：
2.2
作者：
Ruiz, Victoria E.;Sachdev, Monisha;Moss, Steven F.
通讯作者：
Moss, Steven F.