Grell Peter, Borilova Simona, Fabian Pavel, Selingerova Iveta, Novak David, Muller Petr, Kiss Igor, Vyzula Rostislav
Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Zluty kopec 7, 656 53 Brno, Czech Republic.
Department of Comprehensive Cancer Care, Faculty of Medicine, Masaryk University, Kamenice 753/5, 625 00 Brno, Czech Republic.
Cancers (Basel). 2023 Mar 22;15(6):1901. doi: 10.3390/cancers15061901.
Immune checkpoint inhibitors (ICI) are the main therapy currently used in advanced malignant melanoma (MM) and non-small cell lung cancer (NSCLC). Despite the wide variety of uses, the possibility of predicting ICI efficacy in these tumor types is scarce. The aim of our study was to find new predictive biomarkers for ICI treatment. We analyzed, by immunohistochemistry, various cell subsets, including CD3+, CD8+, CD68+, CD20+, and FoxP3+ cells, and molecules such as LAG-3, IDO1, and TGFβ. Comprehensive genomic profiles were analyzed. We evaluated 46 patients with advanced MM (31) and NSCLC (15) treated with ICI monotherapy. When analyzing the malignant melanoma group, shorter median progression-free survival (PFS) was found in tumors positive for nuclear FoxP3 in tumor-infiltrating lymphocytes (TILs) ( = 0.048, HR 3.04) and for CD68 expression ( = 0.034, HR 3.2). Longer PFS was achieved in patients with tumors with PD-L1 TPS ≥ 1 ( = 0.005, HR 0.26). In the NSCLC group, only FoxP3 positivity was associated with shorter PFS and OS. We found that FoxP3 negativity was linked with a better response to ICI in both histological groups.
免疫检查点抑制剂（ICI）是目前用于晚期恶性黑色素瘤（MM）和非小细胞肺癌（NSCLC）的主要治疗方法。尽管其用途广泛，但在这些肿瘤类型中预测ICI疗效的可能性却很有限。我们研究的目的是寻找ICI治疗的新预测生物标志物。我们通过免疫组织化学分析了各种细胞亚群，包括CD3 +、CD8 +、CD68 +、CD20 +和FoxP3 +细胞，以及LAG-3、IDO1和TGFβ等分子。分析了综合基因组图谱。我们评估了46例接受ICI单药治疗的晚期MM（31例）和NSCLC（15例）患者。在分析恶性黑色素瘤组时，发现肿瘤浸润淋巴细胞（TILs）中核FoxP3阳性的肿瘤（= 0.048，HR 3.04）和CD68表达阳性的肿瘤（= 0.034，HR 3.2）的无进展生存期（PFS）中位数较短。PD-L1肿瘤比例评分（TPS）≥1的肿瘤患者的PFS更长（= 0.005，HR 0.26）。在NSCLC组中，只有FoxP3阳性与较短的PFS和总生存期（OS）相关。我们发现，在两个组织学组中，FoxP3阴性均与对ICI的更好反应相关。
