Plasma levels of 12 different cytokines correlate to PD-1 inhibitor combined chemotherapy responses in advanced non-small-cell lung cancer patient

Yun Peng; Qiufeng Qi; Ming Zhu; Yaping Zhang; Yanqing Bao; Yongping Liu

doi:10.1016/j.intimp.2023.110888

Plasma levels of 12 different cytokines correlate to PD-1 inhibitor combined chemotherapy responses in advanced non-small-cell lung cancer patient

Int Immunopharmacol. 2023 Nov;124(Pt A):110888. doi: 10.1016/j.intimp.2023.110888. Epub 2023 Sep 8.

Authors

Yun Peng¹, Qiufeng Qi¹, Ming Zhu¹, Yaping Zhang¹, Yanqing Bao¹, Yongping Liu²

Affiliations

¹ Clinical Oncology Laboratory, Changzhou Tumor Hospital, Changzhou, Jiangsu Province 213002, China.
² Clinical Oncology Laboratory, Changzhou Tumor Hospital, Changzhou, Jiangsu Province 213002, China; Department of Oncology, Changzhou Tumor Hospital, Changzhou, Jiangsu Province 213002, China. Electronic address: liuyongping026@126.com.

PMID: 37690239
DOI: 10.1016/j.intimp.2023.110888

Abstract

Background: Targeted anti-programmed death receptor 1 (PD-1) monoclonal antibodies, when combined with chemotherapy, have shown improved outcomes in non-small cell lung cancer (NSCLC). However, it is important to note that not all patients benefit from this treatment, and there is a pressing need for more reliable efficacy measures and potential predictors of outcome. Cytokines, which are important molecules in the immune system, have been considered as potential biomarkers in clinical settings, but their precise clinical use remains unclear. In this study, our objective was to assess whether the levels of cytokines in the patient's blood sample are associated with tumor response to anti-PD-1 monoclonal antibodies combined with chemotherapy as well as the survival of patients with advanced non-small cell lung cancer.

Materials and methods: A total of 12 plasma cytokines were measured in advanced NSCLC patients (n = 35) and healthy individuals (n = 26) using multi-microsphere flow immunofluorescence. The relationship between cytokine levels and clinical response was analyzed using nonparametric Wilcoxon matched-pair ranked tests. Progression-free survival (PFS) time was recorded for all patients through radiographic outcome assessment and telephone follow-up. Survival curves were generated using the Kaplan-Meier and log-rank tests, and the thresholds for cytokines were determined using receiver operating characteristic analysis (ROC).

Results: The expression levels of interleukin IL-6, IL-1 β, IFN-γ, IL-12p70, and TNF-α were significantly lower in the control group than those in the NSCLC group (p = 0.001, p = 0.0028, p = 0.019, p = 0.0001, p = 0.0021). High IL-10 levels at baseline and after 4 cycles of treatment conferred a worse prognosis; in addition, high TNF-α levels in patients after two cycles of immunochemotherapy suggested drug resistance. High levels of IL-6 and IFN-γ in patients undergoing four cycles of immunochemotherapy were associated with worse PFS.

Conclusions: Our study suggests that cytokines can serve as detection indicators for predicting efficacy in non-small cell lung cancer patients undergoing anti-PD-1 combined with chemotherapy treatment. Elevated levels of IL-10, TNF-α, IL-6, and IFN-γ in the plasma may indicate a higher likelihood of experiencing a worse clinical outcome.