Plasminogen Activating Inhibitor-1 Might Predict the Efficacy of Anti-PD1 Antibody in Advanced Melanoma Patients

被引:14
作者
Ohuchi, Kentaro [1 ]
Kambayashi, Yumi [1 ]
Hidaka, Takanori [1 ]
Fujimura, Taku [1 ]
机构
[1] Tohoku Univ, Grad Sch Med, Dept Dermatol, Sendai, Miyagi, Japan
来源
FRONTIERS IN ONCOLOGY | 2021年 / 11卷
关键词
melanoma; PAI-1; TAMs; Anti-PD1; Abs; efficacy; MACROPHAGES; PROMOTES; CELLS;
D O I
10.3389/fonc.2021.798385
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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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页数:8
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