Plasminogen Activating Inhibitor-1 Might Predict the Efficacy of Anti-PD1 Antibody in Advanced Melanoma Patients.
Plasminogen Activating Inhibitor-1 Might Predict the Efficacy of Anti-PD1 Antibody in Advanced Melanoma Patients.
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DOI：
10.3389/fonc.2021.798385
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发表时间：
2021
影响因子：
4.7
通讯作者：
Fujimura T
中科院分区：
文献类型：
--
作者：
Ohuchi K;Kambayashi Y;Hidaka T;Fujimura T
纤溶酶原激活抑制剂-1 (PAI-1) 在包括黑色素瘤在内的各种癌症的发展中发挥着至关重要的作用。事实上，PAI-1 在癌症进展和转移中的各种促肿瘤功能已被广泛报道。其中，PAI-1 还被报道为通过内吞作用在黑色素瘤细胞上表达 PD-L1 的关键调节因子，导致抗 PD1 抗体 (Abs) 的功效失效。这些发现表明 PAI-1 表达可能预测抗 PD1 抗体的功效。本报告评估了黑色素瘤患者中PAI-1的表达和产生，并在体外研究了PAI-1对肿瘤相关巨噬细胞的免疫调节作用。 PAI-1 的免疫组织化学染色显示，与无反应者相比，反应者黑色素瘤细胞上的 PAI-1 表达显着降低。此外，与无反应者相比，反应者的 PAI-1 基线血清水平显着降低。值得注意的是，PAI-1 在体外减少了单核细胞来源的 M2 巨噬细胞产生的各种趋化因子，这表明 PAI-1 可能会减少肿瘤浸润淋巴细胞，从而阻碍抗 PD1 Ab 的抗肿瘤作用。这些结果表明，PAI-1 的基线血清水平可作为生物标志物，用于识别最有可能从抗黑色素瘤免疫治疗中受益的晚期皮肤黑色素瘤患者。
Plasminogen activating inhibitor-1 (PAI-1) plays crucial roles in the development of various cancers, including melanomas. Indeed, various pro-tumorigenic functions of PAI-1 in cancer progression and metastasis have been widely reported. Among them, PAI-1 is also reported as a key regulator of PD-L1 expression on melanoma cells through endocytosis, leading to abrogating the efficacy of anti-PD1 antibodies (Abs). These findings suggested that PAI-1 expression might predict the efficacy of anti-PD1 Abs. In this report, the expression and production of PAI-1 in melanoma patients were evaluated, and the immunomodulatory effects of PAI-1 on tumor-associated macrophages were investigated in vitro. Immunohistochemical staining of PAI-1 showed that PAI-1 expression on melanoma cells was significantly decreased in responders compared to non-responders. Moreover, baseline serum levels of PAI-1 were significantly decreased in responders compared to non-responders. Notably, PAI-1 decreased the production of various chemokines from monocyte-derived M2 macrophages in vitro, suggesting that PAI-1 might decrease tumor-infiltrating lymphocytes to hamper the anti-tumor effects of anti-PD1 Abs. These results suggest that baseline serum levels of PAI-1 may be useful as a biomarker for identifying patients with advanced cutaneous melanoma most likely to benefit from anti-melanoma immunotherapy.
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影响因子：
8.8
作者：
Kubala, Marta Helena;Punj, Vasu;DeClerck, Yves Albert
通讯作者：
DeClerck, Yves Albert
影响因子：
5.2
作者：
Chen, Shuhai;Morine, Yuji;Shimada, Mitsuo
通讯作者：
Shimada, Mitsuo
影响因子：
3.9
作者：
Fujimura, Taku;Sato, Yota;Aiba, Setsuya
通讯作者：
Aiba, Setsuya
影响因子：
32.4
作者：
Noy, Roy;Pollard, Jeffrey W.
通讯作者：
Pollard, Jeffrey W.
PD-1，PD-1配体的关联以及肿瘤免疫微环境的其他特征与抗PD-1治疗的响应。
DOI：
10.1158/1078-0432.ccr-13-3271
发表时间：
2014-10-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Taube JM;Klein A;Brahmer JR;Xu H;Pan X;Kim JH;Chen L;Pardoll DM;Topalian SL;Anders RA
通讯作者：
Anders RA