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

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...

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Autores principales:	Kentaro Ohuchi, Yumi Kambayashi, Takanori Hidaka, Taku Fujimura
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	melanoma PAI-1 TAMs Anti-PD1 Abs efficacy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/f2cdaabb1655498a93333cfcd2e3169c
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spelling	oai:doaj.org-article:f2cdaabb1655498a93333cfcd2e3169c2021-12-01T11:21:32ZPlasminogen Activating Inhibitor-1 Might Predict the Efficacy of Anti-PD1 Antibody in Advanced Melanoma Patients2234-943X10.3389/fonc.2021.798385https://doaj.org/article/f2cdaabb1655498a93333cfcd2e3169c2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.798385/fullhttps://doaj.org/toc/2234-943XPlasminogen 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.Kentaro OhuchiYumi KambayashiTakanori HidakaTaku FujimuraFrontiers Media S.A.articlemelanomaPAI-1TAMsAnti-PD1 AbsefficacyNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	melanoma PAI-1 TAMs Anti-PD1 Abs efficacy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	melanoma PAI-1 TAMs Anti-PD1 Abs efficacy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Kentaro Ohuchi Yumi Kambayashi Takanori Hidaka Taku Fujimura Plasminogen Activating Inhibitor-1 Might Predict the Efficacy of Anti-PD1 Antibody in Advanced Melanoma Patients
description	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.
format	article
author	Kentaro Ohuchi Yumi Kambayashi Takanori Hidaka Taku Fujimura
author_facet	Kentaro Ohuchi Yumi Kambayashi Takanori Hidaka Taku Fujimura
author_sort	Kentaro Ohuchi
title	Plasminogen Activating Inhibitor-1 Might Predict the Efficacy of Anti-PD1 Antibody in Advanced Melanoma Patients
title_short	Plasminogen Activating Inhibitor-1 Might Predict the Efficacy of Anti-PD1 Antibody in Advanced Melanoma Patients
title_full	Plasminogen Activating Inhibitor-1 Might Predict the Efficacy of Anti-PD1 Antibody in Advanced Melanoma Patients
title_fullStr	Plasminogen Activating Inhibitor-1 Might Predict the Efficacy of Anti-PD1 Antibody in Advanced Melanoma Patients
title_full_unstemmed	Plasminogen Activating Inhibitor-1 Might Predict the Efficacy of Anti-PD1 Antibody in Advanced Melanoma Patients
title_sort	plasminogen activating inhibitor-1 might predict the efficacy of anti-pd1 antibody in advanced melanoma patients
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/f2cdaabb1655498a93333cfcd2e3169c
work_keys_str_mv	AT kentaroohuchi plasminogenactivatinginhibitor1mightpredicttheefficacyofantipd1antibodyinadvancedmelanomapatients AT yumikambayashi plasminogenactivatinginhibitor1mightpredicttheefficacyofantipd1antibodyinadvancedmelanomapatients AT takanorihidaka plasminogenactivatinginhibitor1mightpredicttheefficacyofantipd1antibodyinadvancedmelanomapatients AT takufujimura plasminogenactivatinginhibitor1mightpredicttheefficacyofantipd1antibodyinadvancedmelanomapatients
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Plasminogen Activating Inhibitor-1 Might Predict the Efficacy of Anti-PD1 Antibody in Advanced Melanoma Patients

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