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

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Title: NLRC5/CITA expression correlates with efficient response to checkpoint blockade immunotherapy
Authors: Yoshihama, Sayuri Browse this author
Cho, Steven X. Browse this author
Yeung, Jason Browse this author
Pan, Xuedong Browse this author
Lizee, Gregory Browse this author
Konganti, Kranti Browse this author
Johnson, Valen E. Browse this author
Kobayashi, Koichi S. Browse this author
Issue Date: 5-Feb-2021
Publisher: Nature Research
Journal Title: Scientific reports
Volume: 11
Issue: 1
Start Page: 3258
Publisher DOI: 10.1038/s41598-021-82729-9
PMID: 33547395
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.
Type: article
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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