Co-Treatment of Chloroquine and Trametinib Inhibits Melanoma Cell Proliferation and Decreases Immune Cell Infiltration.
Co-Treatment of Chloroquine and Trametinib Inhibits Melanoma Cell Proliferation and Decreases Immune Cell Infiltration.
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DOI：
10.3389/fonc.2022.782877
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发表时间：
2022
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
--
作者：
自噬被认为是一种细胞保护过程，使用药物活性制剂（如氯喹，CQ）抑制自噬被提议作为一种潜在的癌症辅助治疗方法。在此，我们研究了CQ联合MEK抑制剂曲美替尼（TRA）对黑色素瘤的临床前效果。我们发现CQ和TRA共同处理显著减缓了在Tyr - CreER.BrafCa.Ptenfl/fl小鼠中诱发的黑色素瘤生长。免疫染色显示曲美替尼减少了Ki - 67⁺增殖细胞，并增加了TUNEL⁺凋亡细胞。联合治疗进一步减少了Ki - 67⁺增殖细胞。与体内研究结果一致，CQ和TRA在体外抑制黑色素瘤细胞增殖，这与细胞周期蛋白D1表达降低相关。此外，我们发现用CQ和TRA处理的组织中CD4⁺和CD8⁺ T淋巴细胞以及F4/80⁺巨噬细胞数量显著减少。总之，这些结果表明CQ和TRA共同处理可减少癌细胞增殖，但也会抑制免疫细胞浸润。有必要进一步研究以了解CQ诱导的免疫抑制是否会无意中影响治疗效果。
Autophagy is characterized as a cytoprotective process and inhibition of autophagy with medicinally active agents, such as chloroquine (CQ) is proposed as a prospective adjuvant therapy for cancer. Here, we examined the preclinical effects of CQ combined with the MEK inhibitor trametinib (TRA) on melanoma. We found that cotreatment of CQ and TRA markedly slowed melanoma growth induced in Tyr-CreER.BrafCa.Ptenfl/fl mice. Immunostaining showed that trametinib decreased Ki-67+ proliferating cells, and increased TUNEL+ apoptotic cells. The combo treatment induced a further decrease of Ki-67+ proliferating cells. Consistent with the in vivo findings, CQ and TRA inhibited melanoma cell proliferation in vitro, which was correlated by decreased cyclin D1 expression. In addition, we found that tissues treated with CQ and TRA had significantly decreased numbers of CD4+ and CD8+ T-lymphocytes and F4/80+ macrophages. Together, these results indicate that cotreatment of CQ and TRA decreases cancer cell proliferation, but also dampens immune cell infiltration. Further study is warranted to understand whether CQ-induced immune suppression inadvertently affects therapeutic benefits.
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影响因子：
3.7
作者：
Del Bello B;Toscano M;Moretti D;Maellaro E
通讯作者：
Maellaro E
氯喹通过将肿瘤相关巨噬细胞重置为 M1 表型来调节抗肿瘤免疫反应
影响因子：
16.6
作者：
Chen D;Xie J;Fiskesund R;Dong W;Liang X;Lv J;Jin X;Liu J;Mo S;Zhang T;Cheng F;Zhou Y;Zhang H;Tang K;Ma J;Liu Y;Huang B
通讯作者：
Huang B
DOI：
10.1073/pnas.1607753113
发表时间：
2016-08-23
影响因子：
11.1
作者：
Fattore, Luigi;Mancini, Rita;Ciliberto, Gennaro
通讯作者：
Ciliberto, Gennaro
影响因子：
51.1
作者：
Ascierto, Paolo A.;Schadendorf, Dirk;Dummer, Reinhard
通讯作者：
Dummer, Reinhard
影响因子：
8.8
作者：
Fedorenko, I. V.;Gibney, G. T.;Sondak, V. K.;Smalley, K. S. M.
通讯作者：
Smalley, K. S. M.