An autophagy-dependent anticancer immune response determines the efficacy of melanoma chemotherapy.
An autophagy-dependent anticancer immune response determines the efficacy of melanoma chemotherapy.
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DOI：
10.4161/21624011.2014.944047
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发表时间：
2014
期刊：
影响因子：
7.2
通讯作者：
Kroemer G
中科院分区：
文献类型：
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作者：
Michaud M;Xie X;Bravo-San Pedro JM;Zitvogel L;White E;Kroemer G
有充分的实验和临床证据表明，如果化疗成功地（重新）激活免疫监视，从而引发针对残留肿瘤细胞的长期免疫应答，则化疗更有效。大多数支持这一观点的临床前证据都是从可移植癌症中获得的，对于可移植癌症，已经表明癌细胞中化疗诱导的自噬对于骨髓细胞募集到肿瘤床中以及随后T淋巴细胞介导的肿瘤生长减少是必需的。在这里，我们的特点是由4-羟基-他莫昔芬诱导的表达的Cre重组酶在黑素细胞中，导致在致癌的Braf的激活与失活的肿瘤抑制因子Pten，以及必要的自噬基因Atg 7的任选失活的黑色素瘤的化疗反应。用蒽环类药物米托蒽醌（MTX）进行的全身化疗减少了具有自噬能力的黑素瘤（基因型：BrafCa/+; Ptenfl/fl; Atg 7 +/+）的生长，但未能影响自噬缺陷型黑素瘤（基因型：BrafCa/+; Ptenfl/fl; Atg 7 fl/fl）的进展。MTX对具有自噬能力的黑色素瘤的生长抑制作用被CD 4+或CD 8 + T淋巴细胞的联合耗竭所消除。总之，看来化疗对“自发性”遗传诱导的癌症的成功是由适用于可移植肿瘤的相同规则决定的。
There is ample experimental and clinical evidence that chemotherapies are more efficient if they succeed in (re)activating immune surveillance, hence triggering a long-term immune response against residual tumor cells. Most of the preclinical evidence supporting this notion has been obtained with transplantable cancers, for which it has been shown that chemotherapy-induced autophagy in cancer cells is mandatory for the recruitment of myeloid cells into the tumor bed and the subsequent T lymphocyte-mediated reduction in tumor growth. Here, we characterized the chemotherapeutic response of melanomas caused by 4-hydroxy-tamoxifen-induced expression of the Cre recombinase in melanocytes that results in the activation of oncogenic Braf together with the inactivation of the tumor suppressor Pten, as well as the optional inactivation of the essential autophagy gene Atg7. Systemic chemotherapy with the anthracycline Mitoxantrone (MTX) reduced the growth of autophagy-competent melanomas (genotype: BrafCa/+; Ptenfl/fl; Atg7+/+), yet failed to affect the progression of autophagy-deficient melanomas (genotype: BrafCa/+; Ptenfl/fl; Atg7fl/fl). The growth-inhibitory effect of MTX on autophagy-competent melanomas was abolished by the combined depletion of CD4+ or CD8+ T lymphocytes. In conclusion, it appears that the success of chemotherapy against “spontaneous,” genetically induced cancers is governed by the same rules as those applicable to transplantable tumors.
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DOI：
10.1084/jem.20050915
发表时间：
2005-12-19
期刊：
The Journal of experimental medicine
影响因子：
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作者：
Casares N;Pequignot MO;Tesniere A;Ghiringhelli F;Roux S;Chaput N;Schmitt E;Hamai A;Hervas-Stubbs S;Obeid M;Coutant F;Métivier D;Pichard E;Aucouturier P;Pierron G;Garrido C;Zitvogel L;Kroemer G
通讯作者：
Kroemer G
影响因子：
4.3
作者：
Cartlidge, Robert A.;Thomas, G. R.;McMahon, Martin
通讯作者：
McMahon, Martin
DOI：
10.1083/jcb.200412022
发表时间：
2005-05-09
期刊：
The Journal of cell biology
影响因子：
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作者：
Komatsu M;Waguri S;Ueno T;Iwata J;Murata S;Tanida I;Ezaki J;Mizushima N;Ohsumi Y;Uchiyama Y;Kominami E;Tanaka K;Chiba T
通讯作者：
Chiba T
影响因子：
7.2
作者：
Garg AD;Krysko DV;Vandenabeele P;Agostinis P
通讯作者：
Agostinis P
影响因子：
12.4
作者：
通讯作者：
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