Xagara Anastasia, Goulielmaki Maria, Fortis Sotirios P, Kokkalis Alexandros, Chantzara Evangelia, Christodoulopoulos George, Samaras Ioannis, Saloustros Emmanouil, Tsapakidis Konstantinos, Papadopoulos Vasileios, Pateras Ioannis S, Georgoulias Vasilis, Baxevanis Constantin N, Kotsakis Athanasios
Laboratory of Oncology, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41110 Larissa, Greece.
Cancer Immunology and Immunotherapy Center, Saint Savas Cancer Hospital, 171 Alexandras Ave., 11522 Athens, Greece.
Cancers (Basel). 2024 Jun 28;16(13):2393. doi: 10.3390/cancers16132393.
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 CD3IFNγ 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; = 0.014). PreI patients had significantly higher numbers of possible exhausted CD3CD8PD-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反应的生物标志物可能具有重要的临床意义。我们研究了外周血中预先存在的肿瘤抗原特异性T细胞（PreI）作为非小细胞肺癌（NSCLC）患者免疫治疗预测生物标志物的价值，以及各种循环免疫细胞的频率。纳入了52例初治的III/IV期NSCLC患者，这些患者接受含一线免疫检查点抑制剂（ICI）的治疗方案。PreI通过将外周血单个核细胞（PBMC）与针对四种不同肿瘤相关抗原（TAA）的肽进行体外共培养后，计算CD3IFNγ细胞的百分比来确定。使用多色流式细胞术对外周血免疫细胞进行免疫表型分析。44%的患者检测到PreI T细胞。与PreI阴性患者相比，PreI阳性患者的中位总生存期（OS）显著更长（分别为未达到和321天；P = 0.014）。与PreI阴性患者相比，PreI阳性患者可能耗竭的CD3CD8PD-1细胞数量显著更多，免疫抑制性调节性T细胞（Tregs）的百分比更低。此外，与其他患者相比，PreI阳性且外周血M-MDSC数量低的患者具有显著的生存优势。因此，在NSCLC患者开始ICI治疗前，将预先存在的肿瘤抗原特异性免疫与选定的免疫抑制细胞相结合，可以识别出接受含ICI治疗方案时具有良好临床结局的患者。
