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NLRC5/CITA expression correlates with efficient response to checkpoint blockade immunotherapy
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NLRC5/CITA expression correlates with efficient response to checkpoint blockade immunotherapy
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Journal Article
NLRC5/CITA expression correlates with efficient response to checkpoint blockade immunotherapy
2021
Overview
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.
Publisher
Springer Science and Business Media LLC,Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
