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Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
Published on: July 20, 2019
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Peroxynitrite promotes immune evasion by reducing tumor antigenicity
Aude-Hélène Capietto1, Lélia Delamarre1
1Cancer Immunology, Genentech, 1 DNA way, South San Francisco, CA 94080, USA.
Cell Reports. Medicine
|October 19, 2022
Summary
Peroxynitrite, an oxidant in tumors, alters tumor cell peptide presentation and hinders immune recognition. Inhibiting this oxidant alongside immune checkpoint blockade improves cancer treatment efficacy in preclinical studies.
Area of Science:
- Immunology
- Oncology
- Biochemistry
Background:
- The tumor microenvironment (TME) contains various factors that influence cancer progression and immune evasion.
- Peroxynitrite is an oxidant commonly found in the TME, but its specific role in modulating tumor antigen presentation and immune recognition is not fully understood.
Purpose of the Study:
- To investigate the impact of peroxynitrite on the presentation of MHC class I peptides by tumor cells.
- To evaluate the therapeutic potential of combining peroxynitrite inhibition with immune checkpoint blockade.
Main Methods:
- Analysis of MHC class I peptide repertoires in tumor cells exposed to peroxynitrite.
- Preclinical models to assess the efficacy of combined peroxynitrite inhibition and immune checkpoint blockade therapies.
Main Results:
- Peroxynitrite significantly alters the repertoire of MHC class I peptides presented by tumor cells.
- This alteration by peroxynitrite limits the recognition of tumor cells by the immune system.
- Combined inhibition of peroxynitrite and immune checkpoint blockade demonstrated enhanced anti-tumor efficacy in preclinical settings.
Conclusions:
- Peroxynitrite plays a critical role in tumor immune evasion by modifying tumor antigen presentation.
- Targeting peroxynitrite in combination with immune checkpoint inhibitors represents a promising therapeutic strategy for cancer treatment.
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