Correlation between oxidative stress and immune profiles during immunotherapy in metastatic non-oncogene addicted NSCLC patients.

Oxidative stress is considered one of the cancer hallmarks, affecting tumor initiation, progression, and metastasis. High levels of reactive oxygen species (ROS) compromise 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 measured by ELISA. Twenty-seven healthy donors served as controls. The data indicated that cancer patients had higher levels of sNox2-dp compared to healthy donors (p< 0.0001). Elevated sNox2-dp levels were linked with inflammation-related comorbidities (p=0.008) and platelet counts (p=0.03) in NSCLC patients. Additionally, sNox2-dp showed a negative correlation with immune cells involved in activation, such as proliferating (Ki67+) CD8+, PD1+, and effector lymphocytes, and a positive association with immunosuppressive PMN-MDSCs and inflammatory soluble immune factors, such as IL1a, IL1b, 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 might be indirectly influenced by immunotherapy and could serve as an innovative tool to identify responding patients in the NSCLC setting.