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Article
2023
NLRC5-CIITA fusion protein as an effective inducer of MHC-I expression and antitumor immunity
NLRC5-CIITA fusion protein as an effective inducer of MHC-I expression and antitumor immunity
Abstract (English)
Aggressive tumors evade cytotoxic T lymphocytes by suppressing MHC class-I (MHC-I) expression that also compromises tumor responsiveness to immunotherapy. MHC-I defects strongly correlate to defective expression of NLRC5, the transcriptional activator of MHC-I and antigen processing genes. In poorly immunogenic B16 melanoma cells, restoring NLRC5 expression induces MHC-I and elicits antitumor immunity, raising the possibility of using NLRC5 for tumor immunotherapy. As the clinical application of NLRC5 is constrained by its large size, we examined whether a smaller NLRC5-CIITA fusion protein, dubbed NLRC5-superactivator (NLRC5-SA) as it retains the ability to induce MHC-I, could be used for tumor growth control. We show that stable NLRC5-SA expression in mouse and human cancer cells upregulates MHC-I expression. B16 melanoma and EL4 lymphoma tumors expressing NLRC5-SA are controlled as efficiently as those expressing full-length NLRC5 (NLRC5-FL). Comparison of MHC-I-associated peptides (MAPs) eluted from EL4 cells expressing NLRC5-FL or NLRC5-SA and analyzed by mass spectrometry revealed that both NLRC5 constructs expanded the MAP repertoire, which showed considerable overlap but also included a substantial proportion of distinct peptides. Thus, we propose that NLRC5-SA, with its ability to increase tumor immunogenicity and promote tumor growth control, could overcome the limitations of NLRC5-FL for translational immunotherapy applications.
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International journal of molecular sciences, 24 (2023), 8, 7206.
https://doi.org/10.3390/ijms24087206.
ISSN: 1422-0067
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610 Medicine and health
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@article{Santharam2023,
url = {https://hohpublica.uni-hohenheim.de/handle/123456789/16332},
doi = {10.3390/ijms24087206},
author = {Santharam, Madanraj Appiya and Shukla, Akhil and Levesque, Dominique et al.},
title = {NLRC5-CIITA fusion protein as an effective inducer of MHC-I expression and antitumor immunity},
journal = {International journal of molecular sciences},
year = {2023},
volume = {24},
number = {8},
}