T-cell-mediated anti-tumoral responses may have significant clinical relevance as a biomarker for response to immunotherapy. The value of peripheral blood pre-existing tumor antigen-specific T cells (PreI+) as a predictive immunotherapy biomarker in NSCLC patients was investigated, along with the frequency of various circulating immune cells. Fifty-two treatment-naïve, stage III/IV NSCLC patients, treated with front-line immune checkpoint inhibitors (ICI)-containing regimens were enrolled. PreI was calculated as the percentages of CD3+IFNγ+cells after in vitro co-cultures of PBMCs with peptides against four different Tumor-Associated Antigens (TAA). Immunophenotyping of peripheral blood immune cells was performed using multicolor flow cytometry. PreI+T cells were detected in 44% of patients. Median overall survival (OS) was significantly higher in PreI+patients compared to PreI–patients (not reached vs. 321 days, respectively;p= 0.014). PreI+patients had significantly higher numbers of possible exhausted CD3+CD8+PD-1+cells and lower percentages of immunosuppressive Tregs compared to PreI−patients. Additionally, patients with PreI+and low numbers of peripheral blood M-MDSCs had a significant survival advantage compared to the rest of the patients. Thus, combining pre-existing tumor antigen-specific immunity before initiation of ICI in NSCLC patients with selected immune-suppressive cells could identify patients who have a favorable clinical outcome when treated with ICI-containing regimens.
T细胞介导的抗肿瘤反应作为免疫治疗疗效的生物标志物可能具有重要临床意义。本研究探讨了非小细胞肺癌（NSCLC）患者外周血中预先存在的肿瘤抗原特异性T细胞（PreI+）作为免疫治疗预测性生物标志物的价值，并分析了各类循环免疫细胞的频率。研究纳入52例初治III/IV期NSCLC患者，均接受含一线免疫检查点抑制剂（ICI）方案治疗。通过外周血单个核细胞与四种不同肿瘤相关抗原（TAA）肽段体外共培养，计算CD3+IFNγ+细胞百分比作为PreI值。采用多色流式细胞术对外周血免疫细胞进行免疫表型分析。结果显示44%的患者检测到PreI+T细胞。PreI+患者的中位总生存期（OS）显著高于PreI-患者（未达到 vs. 321天，p=0.014）。与PreI-患者相比，PreI+患者体内可能耗竭的CD3+CD8+PD-1+细胞数量显著更高，而免疫抑制性调节性T细胞（Tregs）比例显著降低。此外，同时具备PreI+特征且外周血单核髓源性抑制细胞（M-MDSCs）数量较低的患者，其生存优势较其他患者更为显著。因此，在NSCLC患者开始ICI治疗前，综合评估其既有的肿瘤抗原特异性免疫状态及特定免疫抑制细胞水平，可有效筛选出适合接受含ICI方案治疗且预后良好的患者群体。
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