Correlation Between Oxidative Stress and Immune Profiles During Immunotherapy in Metastatic Non-Oncogene-Addicted
Mariangela Peruzzi1,2, Lucrezia Tuosto3, Alain Gelibter4
1Department of Medical and Cardiovascular Sciences, Sapienza University of Rome, 00185 Rome, Italy.
Abstract:
Oxidative stress is considered one of the cancer hallmarks, influencing tumor initiation, progression, and metastasis. High levels of reactive oxygen species (ROS) impair the effectiveness of the immune response in cancer patients. We examined changes in oxidative stress during immunotherapy, exploring the relationship between the immune system and clinical parameters related to oxidative burden. Several T-cell and myeloid subsets from 79 metastatic non-oncogene-addicted non-small-cell lung cancer (NSCLC) patients were analyzed using flow cytometry. Additionally, 20 cytokines were measured in serum samples, and sNox2-dp levels, an indicator of NOX2 activity, were assessed by ELISA. Seventy-nine healthy donors served as controls. The data showed that cancer patients had higher levels of sNox2-dp compared to healthy donors (p < 0.0001). Elevated sNox2-dp levels were associated with inflammation-related comorbidities (p = 0.008) and platelet counts (p = 0.03) in NSCLC patients. Furthermore, sNox2-dp displayed a negative correlation with immune cells involved in activation, such as proliferating (Ki67+) CD8+, PD1+ and effector lymphocytes, and a positive correlation with immunosuppressive PMN-MDSCs and inflammatory soluble immune factors, including IL1α, IL1β, IL6, IL10, CCL3, and CCL4. Oxidation levels decreased after immunotherapy (p = 0.04) and increased only in non-responder patients (p = 0.02). Oxidative stress may be indirectly affected by immunotherapy and could serve as a novel tool to identify responding patients in the NSCLC setting.
Insights
Oxidative stress, indicated by sNox2-dp, is elevated in non-small-cell lung cancer (NSCLC) patients and correlates with immune suppression. Immunotherapy reduced oxidative stress in responders, suggesting its potential as a biomarker.
Area of Science:
- Immunology
- Oncology
- Biochemistry
Background:
- Oxidative stress is a hallmark of cancer, impacting tumor progression and immune response.
- High reactive oxygen species (ROS) levels can hinder anti-cancer immunity.
Purpose of the Study:
- To investigate oxidative stress changes during cancer immunotherapy.
- To explore the link between the immune system, oxidative burden, and clinical factors in NSCLC.
Main Methods:
- Flow cytometry analyzed immune cell subsets in 79 metastatic NSCLC patients.
- Cytokine levels and sNox2-dp (NOX2 activity indicator) were measured.
- Data compared patients to 79 healthy donors and analyzed changes post-immunotherapy.
Main Results:
- NSCLC patients exhibited higher sNox2-dp levels than controls, associated with inflammation and platelet counts.
- Elevated sNox2-dp correlated with suppressed immune cells (e.g., CD8+ T cells) and increased immunosuppressive cells (PMN-MDSCs).
- Oxidative stress decreased post-immunotherapy, but increased in non-responders, suggesting immunotherapy's influence.
Conclusions:
- Oxidative stress is linked to immune dysfunction in NSCLC.
- Immunotherapy may modulate oxidative stress levels.
- sNox2-dp could be a novel biomarker for predicting immunotherapy response in NSCLC.
