Immune cells have the potential to control the growth of tumor. However, this effect could be offset by immunosuppression associated with an increased production of reactive oxygen species. Multiple studies indicate that the antitumor effect of immune cells is correlated with their antioxidant capacity. This review discusses the role of reactive oxygen species in the tumor microenvironment by describing their distinct effects on different immune cells, including myeloid-derived suppressor cells, regulatory T cells, tumor-associated macrophages, cytotoxic T lymphocytes, natural killer cells, and dendritic cells. In the end, we conclude with the prospect of treatment for cancer by targeting antioxidant defense in immune cells.

Human epidermal growth factor receptor‑2 (HER2) negative advanced gastric cancer (GC) has a high global incidence and mortality rate with limited options for second‑line treatment. Monotherapy is not effective and the combination of chemotherapy and immunotherapy has not yet been included in the guidelines. The present study aimed to explore a new treatment approach by conducting a single‑center, retrospective, observational real‑world study. A total of 21 patients with advanced HER2‑negative GC, who had progressed after receiving standard first‑line regimens [tegafur, gimeracil and oteracil potassium capsules (S‑1) or capecitabine plus oxaliplatin], were selected. The application of programmed cell death‑1 (PD‑1) inhibitor combined with taxanes was selected as the second‑line treatment. The primary outcomes measured were progression‑free survival (PFS), pathological complete response, objective response rate (ORR), disease control rate (DCR) and adverse reactions in the present patient cohort. The median (m)PFS in the overall population was 7.1 months, with a 95% confidence interval (CI) of 6.0‑8.2 months and the median overall survival (mOS) was 11.3 months, with a 95% CI of 4.5‑18.2 months. The ORR was 9.5% and the DCR was 90.5%. Univariate and multivariate analyses indicated that Ki67 <70% and tumor marker‑positive status [one or two increases among carcinoembryogenic antigen (CEA), cancer antigen (CA) 199 and CA125] were independent prognostic factors for PFS and overall survival (OS) in second‑line treatment. Significant statistical differences were noted in PFS (mPFS=5.3 months, 95% CI: 3.1‑7.5 months vs. mPFS=9.1 months, 95% CI: 6.2‑12.0 months; P=0.002) and OS (mOS=8.8 months, 95% CI: 7.0‑10.7 months vs. mOS=17.2 months, 95% CI: 16.0‑18.5 months; P=0.013) between the Ki67‑high group (Ki67 ≥70%) and the Ki67‑low group (Ki67 <70%). Significant statistical differences were noted in OS between tumor marker‑negative status (CEA, CA199 and CA125 within normal range) and tumor marker‑positive status (one or two increases among CEA, CA199 and CA125; mOS=17.2 months, 95% CI: 16.0‑18.4 months vs. mOS=8.8 months, 95% CI: 5.3‑12.4 months; P=0.018); however, no significant differences were noted in PFS between these two groups. The present study retrospectively analyzed the new second‑line approach of PD‑1 inhibitor combined with taxanes for HER2 negative GC which effectively improved patient PFS and OS compared with single‑agent chemotherapy. The expression levels of Ki67 and the tumor marker‑negative status possess potential clinical value in monitoring prognosis and guiding future individualized use of chemotherapy combined with immunotherapy.