Related Experiment Video
Updated: Nov 18, 2025
Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
NLRC5/CITA expression correlates with efficient response to checkpoint blockade immunotherapy
Sayuri Yoshihama1,2, Steven X Cho3, Jason Yeung1
1Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, 415A Reynolds Medical Building, College Station, TX, 77843, USA.
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.
Insights
NLRC5 expression predicts response to cancer immunotherapy. Higher NLRC5 levels in melanoma tumors correlate with better outcomes from checkpoint blockade therapies like anti-CTLA-4 and anti-PD1.
Area of Science:
- Immunology
- Oncology
- Genetics
Background:
- Checkpoint blockade immunotherapy shows promise for various cancers.
- Cancer cells can evade immune detection, limiting immunotherapy effectiveness.
- Identifying suitable patients is vital due to treatment costs and side effects.
Purpose of the Study:
- To investigate NLRC5 as a predictive biomarker for checkpoint blockade immunotherapy response.
- To evaluate NLRC5 expression in relation to anti-CTLA-4 and anti-PD1 therapies in melanoma.
Main Methods:
- Analysis of NLRC5 and MHC class I gene expression in melanoma tumors from immunotherapy responders and non-responders.
- Multivariate analysis incorporating tumor mutation number, neo-antigen load, and PD-L2 expression.
- Correlation of NLRC5 expression/methylation and mutation load with patient survival.
Main Results:
- Melanoma patients responding to immunotherapy had higher NLRC5 and MHC class I gene expression.
- Multivariate analysis improved stratification of responders versus non-responders to anti-CTLA-4 therapy.
- NLRC5 expression and tumor mutation load significantly correlated with increased patient survival.
Conclusions:
- NLRC5 tumor expression is a potential predictive biomarker for anti-CTLA-4 and anti-PD1 immunotherapy response in melanoma.
- Combined assessment of NLRC5 and tumor mutation load may offer valuable prognostic insights.
- These findings could guide patient selection for immunotherapy, optimizing treatment efficacy and resource allocation.
More Related Videos
08:04In Vitro Tumor Cell Rechallenge For Predictive Evaluation of Chimeric Antigen Receptor T Cell Antitumor Function
Published on: February 27, 2019
10:29Semi-automatic PD-L1 Characterization and Enumeration of Circulating Tumor Cells from Non-small Cell Lung Cancer Patients by Immunofluorescence
Published on: August 14, 2019