Predictive value of dynamic monitoring of Th1/Th2/Th17 cytokines for treatment response and prognosis in patients with stage Ⅲ-Ⅳ LSCC receiving first-line immunotherapy combined with chemotherapy: a retrospective study
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Abstract:
[Abstract] Objective: To investigate the dynamic changes and predictive value of peripheral blood T helper 1 (Th1)/Th2/Th17-related cytokines IL-2, IL-4, IL-6, IL-10, IFN-γ, TNF-α, and IL-17A for treatment efficacy and prognosis in patients with stage Ⅲ-Ⅳ lung squamous cell carcinoma (LSCC) undergoing first-line immunotherapy combined with chemotherapy. Methods: Clinical data of 58 patients with stage Ⅲ-Ⅳ LSCC who received first-line immunotherapy combined with chemotherapy at the Affiliated Hospital of Inner Mongolia Medical University from January 2020 to December 2023 were retrospectively analyzed. Peripheral blood samples were collected at baseline, after 2, 4, and 6 treatment cycles, and at disease progression. Th1/Th2/Th17 cytokine levels were measured using flow cytometry. Receiver operating characteristic (ROC) curves were used to determine optimal baseline cut-off values, based on which patients were divided into high- and low-expression groups. According to RECIST 1.1 criteria, patients were categorized into objective response rate (ORR; complete remission [CR] + partial remission [PR]) and non-ORR (stable disease [SD]+ progressive disease [PD]) groups, as well as disease control rate (DCR; CR+PR+SD) and non-DCR (PD) groups. Based on PD-L1 expression scores, patients were divided into PD-L1 ≥ 1% and PD-L1<1% or unknown groups. Differences in treatment efficacy between groups were compared, and correlations between clinicopathological characteristics and efficacy were analyzed. Generalized estimating equations (GEE) were used to assess the relationship between cytokine dynamics and treatment efficacy. Survival curves were plotted using the Kaplan-Meier method, with Log-rank tests for intergroup comparisons. Univariate and multivariate prognostic analyses were performed using COX proportional hazards regression. Results: Patients with high baseline IL-2 or IFN-γ expression demonstrated significantly higher ORRs than those with low expression (P < 0.001). The DCRs were significantly higher in the IL-2-high, IFN-γ-high, IL-10-low, and TNF-α-low groups compared with their counterparts (P < 0.001). The DCRs were significantly higher in patients with PD-L1 ≥ 1% than those with PD-L1 < 1% or unknown group (P < 0.001). Dynamic analysis revealed that serum IL-6 levels at cycles 4 and 6 were significantly lower in the response group and disease-controlled group compared with the non-response group and uncontrolled group (P < 0.05 or P < 0.001). IFN- γ levels were significantly higher in the response group than in the non-response group at baseline and cycle 6 (P < 0.05), and higher in disease-controlled group than in the uncontrolled group at baseline (P < 0.05). Survival analysis showed significantly shorter median progression-free survival (PFS) in patients with low IL-2, high IL-10, high TNF- α, and low IFN- γ expression (all P < 0.05). Multivariate COX analysis identified baseline IL-2 < 2.45 pg/mL and IL-10 ≥ 3.52 pg/mL as independent risk factors for PFS. Conclusion: Baseline levels and dynamic changes of peripheral blood Th1/Th2/Th17 cell-related cytokines have predictive value for treatment efficacy and prognosis in patients with stage Ⅲ–Ⅳ LSCC receiving first-line immunotherapy combined with chemotherapy.