Tetrathiomolybdate (TM)-associated copper depletion influences collagen remodeling and immune response in the pre-metastatic niche of breast cancer.
Tetrathiomolybdate (TM)-associated copper depletion influences collagen remodeling and immune response in the pre-metastatic niche of breast cancer.
复制标题
DOI：
10.1038/s41523-021-00313-w
复制
发表时间：
2021-08-23
影响因子：
5.9
通讯作者：
Vahdat LT
中科院分区：
文献类型：
--
作者：
Liu YL;Bager CL;Willumsen N;Ramchandani D;Kornhauser N;Ling L;Cobham M;Andreopoulou E;Cigler T;Moore A;LaPolla D;Fitzpatrick V;Ward M;Warren JD;Fischbach C;Mittal V;Vahdat LT
四硫代钼酸盐（TM）是一种新型的铜消耗化合物，在高风险和三阴性乳腺癌患者的II期研究中与有希望的生存相关。我们试图阐明TM的机制，探讨其对胶原蛋白加工和免疫功能的肿瘤微环境（TME）的影响。使用探索性队列，我们确定了乳腺癌患者与对照组之间不同的胶原蛋白加工标志物（LOXL 2，PRO-C3，C6 M和C1 M）。我们在II期研究中测量了TM治疗患者中的这些胶原蛋白生物标志物，并检测到与经历疾病进展的患者相比，无疾病患者中胶原蛋白交联减少和过度形成降解增加的证据。临床前研究显示，与对照组相比，TM治疗组小鼠的胶原沉积减少，髓源性抑制细胞水平降低，CD 4 + T细胞浸润增加。这项研究揭示了TM靶向TME和免疫应答的新机制，具有跨癌症类型的潜在应用。
Tetrathiomolybdate (TM) is a novel, copper-depleting compound associated with promising survival in a phase II study of patients with high-risk and triple-negative breast cancer. We sought to elucidate the mechanism of TM by exploring its effects on collagen processing and immune function in the tumor microenvironment (TME). Using an exploratory cohort, we identified markers of collagen processing (LOXL2, PRO-C3, C6M, and C1M) that differed between those with breast cancer versus controls. We measured these collagen biomarkers in TM-treated patients on the phase II study and detected evidence of decreased collagen cross-linking and increased degradation over formation in those without disease compared to those who experienced disease progression. Preclinical studies revealed decreased collagen deposition, lower levels of myeloid-derived suppressor cells, and higher CD4+ T-cell infiltration in TM-treated mice compared with controls. This study reveals novel mechanisms of TM targeting the TME and immune response with potential applications across cancer types.
登录
查看更多内容
影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
影响因子：
254.7
作者：
DeSantis, Carol E.;Fedewa, Stacey A.;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
影响因子：
3.8
作者：
Jain S;Ward MM;O'Loughlin J;Boeck M;Wiener N;Chuang E;Cigler T;Moore A;Donovan D;Lam C;Cobham MV;Schneider S;Christos P;Baergen RN;Swistel A;Lane ME;Mittal V;Rafii S;Vahdat LT
通讯作者：
Vahdat LT
DOI：
10.1039/c5ib00040h
发表时间：
2015-10
期刊：
Integrative biology : quantitative biosciences from nano to macro
影响因子：
--
作者：
Acerbi I;Cassereau L;Dean I;Shi Q;Au A;Park C;Chen YY;Liphardt J;Hwang ES;Weaver VM
通讯作者：
Weaver VM
影响因子：
45.3
作者：
Allison, Kimberly H.;Hammond, M. Elizabeth H.;Wolff, Antonio C.
通讯作者：
Wolff, Antonio C.