NLRC5/CITA expression correlates with efficient response to checkpoint blockade immunotherapy

Abstract Checkpoint blockade-mediated immunotherapy is emerging as an effective treatment modality for multiple cancer types. However, cancer cells frequently evade the immune system, compromising the effectiveness of immunotherapy. It is crucial to develop screening methods to identify the patients...

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Autores principales:	Sayuri Yoshihama, Steven X. Cho, Jason Yeung, Xuedong Pan, Gregory Lizee, Kranti Konganti, Valen E. Johnson, Koichi S. Kobayashi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/de1241d0f963406ab60cbcf3271651f4
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spelling	oai:doaj.org-article:de1241d0f963406ab60cbcf3271651f42021-12-02T10:44:14ZNLRC5/CITA expression correlates with efficient response to checkpoint blockade immunotherapy10.1038/s41598-021-82729-92045-2322https://doaj.org/article/de1241d0f963406ab60cbcf3271651f42021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82729-9https://doaj.org/toc/2045-2322Abstract Checkpoint blockade-mediated immunotherapy is emerging as an effective treatment modality for multiple cancer types. However, cancer cells frequently evade the immune system, compromising the effectiveness of immunotherapy. It is crucial to develop screening methods to identify the patients who would most benefit from these therapies because of the risk of the side effects and the high cost of treatment. Here we show that expression of the MHC class I transactivator (CITA), NLRC5, is important for efficient responses to anti-CTLA-4 and anti-PD1 checkpoint blockade therapies. Melanoma tumors derived from patients responding to immunotherapy exhibited significantly higher expression of NLRC5 and MHC class I-related genes compared to non-responding patients. In addition, multivariate analysis that included the number of tumor-associated non-synonymous mutations, predicted neo-antigen load and PD-L2 expression was capable of further stratifying responders and non-responders to anti-CTLA4 therapy. Moreover, expression or methylation of NLRC5 together with total somatic mutation number were significantly correlated with increased patient survival. These results suggest that NLRC5 tumor expression, alone or together with tumor mutation load constitutes a valuable predictive biomarker for both prognosis and response to anti-CTLA-4 and potentially anti-PD1 blockade immunotherapy in melanoma patients.Sayuri YoshihamaSteven X. ChoJason YeungXuedong PanGregory LizeeKranti KongantiValen E. JohnsonKoichi S. KobayashiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sayuri Yoshihama Steven X. Cho Jason Yeung Xuedong Pan Gregory Lizee Kranti Konganti Valen E. Johnson Koichi S. Kobayashi NLRC5/CITA expression correlates with efficient response to checkpoint blockade immunotherapy
description	Abstract Checkpoint blockade-mediated immunotherapy is emerging as an effective treatment modality for multiple cancer types. However, cancer cells frequently evade the immune system, compromising the effectiveness of immunotherapy. It is crucial to develop screening methods to identify the patients who would most benefit from these therapies because of the risk of the side effects and the high cost of treatment. Here we show that expression of the MHC class I transactivator (CITA), NLRC5, is important for efficient responses to anti-CTLA-4 and anti-PD1 checkpoint blockade therapies. Melanoma tumors derived from patients responding to immunotherapy exhibited significantly higher expression of NLRC5 and MHC class I-related genes compared to non-responding patients. In addition, multivariate analysis that included the number of tumor-associated non-synonymous mutations, predicted neo-antigen load and PD-L2 expression was capable of further stratifying responders and non-responders to anti-CTLA4 therapy. Moreover, expression or methylation of NLRC5 together with total somatic mutation number were significantly correlated with increased patient survival. These results suggest that NLRC5 tumor expression, alone or together with tumor mutation load constitutes a valuable predictive biomarker for both prognosis and response to anti-CTLA-4 and potentially anti-PD1 blockade immunotherapy in melanoma patients.
format	article
author	Sayuri Yoshihama Steven X. Cho Jason Yeung Xuedong Pan Gregory Lizee Kranti Konganti Valen E. Johnson Koichi S. Kobayashi
author_facet	Sayuri Yoshihama Steven X. Cho Jason Yeung Xuedong Pan Gregory Lizee Kranti Konganti Valen E. Johnson Koichi S. Kobayashi
author_sort	Sayuri Yoshihama
title	NLRC5/CITA expression correlates with efficient response to checkpoint blockade immunotherapy
title_short	NLRC5/CITA expression correlates with efficient response to checkpoint blockade immunotherapy
title_full	NLRC5/CITA expression correlates with efficient response to checkpoint blockade immunotherapy
title_fullStr	NLRC5/CITA expression correlates with efficient response to checkpoint blockade immunotherapy
title_full_unstemmed	NLRC5/CITA expression correlates with efficient response to checkpoint blockade immunotherapy
title_sort	nlrc5/cita expression correlates with efficient response to checkpoint blockade immunotherapy
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/de1241d0f963406ab60cbcf3271651f4
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NLRC5/CITA expression correlates with efficient response to checkpoint blockade immunotherapy

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