Topical arginase inhibition decreases growth of cutaneous squamous cell carcinoma

Abstract Cutaneous squamous cell carcinomas (cSCC) are among the most commonly diagnosed malignancies, causing significant morbidity and mortality. Tumor-associated macrophage (TAM) expression of arginase is implicated in tumor progression, and therapeutic use of arginase inhibitors has been studied...

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Autores principales:	Amit Mittal, Mike Wang, Aurobind Vidyarthi, Diana Yanez, Gabriela Pizzurro, Durga Thakral, Erin Tracy, Oscar R. Colegio
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/96e8c37bc01d4a76b19b76c4448d098c
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spelling	oai:doaj.org-article:96e8c37bc01d4a76b19b76c4448d098c2021-12-02T14:47:31ZTopical arginase inhibition decreases growth of cutaneous squamous cell carcinoma10.1038/s41598-021-90200-y2045-2322https://doaj.org/article/96e8c37bc01d4a76b19b76c4448d098c2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90200-yhttps://doaj.org/toc/2045-2322Abstract Cutaneous squamous cell carcinomas (cSCC) are among the most commonly diagnosed malignancies, causing significant morbidity and mortality. Tumor-associated macrophage (TAM) expression of arginase is implicated in tumor progression, and therapeutic use of arginase inhibitors has been studied in various cancers. However, investigating potential cSCC immunotherapies including arginase inhibition in pre-clinical models is hampered by the lack of appropriate tumor models in immunocompetent mice. PDV is a cSCC cell line derived from chemical carcinogenesis of mouse keratinocytes. PDVC57 cells were derived from a PDV tumor in C57BL/6 (B6) mice. Unlike PDV, PDVC57 tumors grow consistently in B6 mice, and have increased TAMs, decreased dendritic and T cell intra-tumor infiltration. Arginase inhibition in cSCC tumors using Nω-hydroxy-nor-arginine (nor-NOHA) reduced tumor growth in B6 mice but not immunodeficient Rag1-deficient mice. nor-NOHA administration increased dendritic and T cell tumor-infiltration and PD-1 expression. The combination of nor-NOHA and anti-PD-1 therapy with nivolumab enhanced anti-PD-1 therapeutic efficacy. This study demonstrates the therapeutic potential of transcutaneous arginase inhibition in cSCC. A competent immune microenvironment is required for tumor growth inhibition using this arginase inhibitor. Synergistic co-inhibition of tumor growth in these results, supports further examination of transcutaneous arginase inhibition as a therapeutic modality for cSCC.Amit MittalMike WangAurobind VidyarthiDiana YanezGabriela PizzurroDurga ThakralErin TracyOscar R. ColegioNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Amit Mittal Mike Wang Aurobind Vidyarthi Diana Yanez Gabriela Pizzurro Durga Thakral Erin Tracy Oscar R. Colegio Topical arginase inhibition decreases growth of cutaneous squamous cell carcinoma
description	Abstract Cutaneous squamous cell carcinomas (cSCC) are among the most commonly diagnosed malignancies, causing significant morbidity and mortality. Tumor-associated macrophage (TAM) expression of arginase is implicated in tumor progression, and therapeutic use of arginase inhibitors has been studied in various cancers. However, investigating potential cSCC immunotherapies including arginase inhibition in pre-clinical models is hampered by the lack of appropriate tumor models in immunocompetent mice. PDV is a cSCC cell line derived from chemical carcinogenesis of mouse keratinocytes. PDVC57 cells were derived from a PDV tumor in C57BL/6 (B6) mice. Unlike PDV, PDVC57 tumors grow consistently in B6 mice, and have increased TAMs, decreased dendritic and T cell intra-tumor infiltration. Arginase inhibition in cSCC tumors using Nω-hydroxy-nor-arginine (nor-NOHA) reduced tumor growth in B6 mice but not immunodeficient Rag1-deficient mice. nor-NOHA administration increased dendritic and T cell tumor-infiltration and PD-1 expression. The combination of nor-NOHA and anti-PD-1 therapy with nivolumab enhanced anti-PD-1 therapeutic efficacy. This study demonstrates the therapeutic potential of transcutaneous arginase inhibition in cSCC. A competent immune microenvironment is required for tumor growth inhibition using this arginase inhibitor. Synergistic co-inhibition of tumor growth in these results, supports further examination of transcutaneous arginase inhibition as a therapeutic modality for cSCC.
format	article
author	Amit Mittal Mike Wang Aurobind Vidyarthi Diana Yanez Gabriela Pizzurro Durga Thakral Erin Tracy Oscar R. Colegio
author_facet	Amit Mittal Mike Wang Aurobind Vidyarthi Diana Yanez Gabriela Pizzurro Durga Thakral Erin Tracy Oscar R. Colegio
author_sort	Amit Mittal
title	Topical arginase inhibition decreases growth of cutaneous squamous cell carcinoma
title_short	Topical arginase inhibition decreases growth of cutaneous squamous cell carcinoma
title_full	Topical arginase inhibition decreases growth of cutaneous squamous cell carcinoma
title_fullStr	Topical arginase inhibition decreases growth of cutaneous squamous cell carcinoma
title_full_unstemmed	Topical arginase inhibition decreases growth of cutaneous squamous cell carcinoma
title_sort	topical arginase inhibition decreases growth of cutaneous squamous cell carcinoma
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/96e8c37bc01d4a76b19b76c4448d098c
work_keys_str_mv	AT amitmittal topicalarginaseinhibitiondecreasesgrowthofcutaneoussquamouscellcarcinoma AT mikewang topicalarginaseinhibitiondecreasesgrowthofcutaneoussquamouscellcarcinoma AT aurobindvidyarthi topicalarginaseinhibitiondecreasesgrowthofcutaneoussquamouscellcarcinoma AT dianayanez topicalarginaseinhibitiondecreasesgrowthofcutaneoussquamouscellcarcinoma AT gabrielapizzurro topicalarginaseinhibitiondecreasesgrowthofcutaneoussquamouscellcarcinoma AT durgathakral topicalarginaseinhibitiondecreasesgrowthofcutaneoussquamouscellcarcinoma AT erintracy topicalarginaseinhibitiondecreasesgrowthofcutaneoussquamouscellcarcinoma AT oscarrcolegio topicalarginaseinhibitiondecreasesgrowthofcutaneoussquamouscellcarcinoma
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Topical arginase inhibition decreases growth of cutaneous squamous cell carcinoma

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