Miao Xiaoyan, Guo Ziyi, Zhang Kai, Chang Jin, Yang Jianmin, Miao Guoying, Tian Yan
Department of Plastic Surgery, Affiliated Hospital of Hebei Engineering University, Handan, Hebei 056002, P.R. China.
Department of Burn and Plastic Surgery, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China.
Oncol Lett. 2024 Jul 12;28(3):433. doi: 10.3892/ol.2024.14566. eCollection 2024 Sep.
Advanced melanoma is an aggressive and dangerous form of skin cancer, and programmed cell death-1 (PD-1) inhibitors are recommended treatment options for patients with advanced melanoma. Mucosa-associated lymphoid tissue 1 (MALT1) impairs CD8 T-cell activation to induce immune escape, leading to a reduction in the antitumor effect of PD-1 inhibitors. The present study aimed to assess the prognostic implication of MALT1 in patients with advanced melanoma receiving PD-1 inhibitor monotherapy. Blood MALT1 levels were assessed using reverse transcription-quantitative PCR in 20 healthy controls (HCs) after enrollment and in 49 patients with advanced melanoma before (T), as well as 2 months (T) and 4 months after (T) PD-1 inhibitor monotherapy. The maximum level of MALT1 in HCs (3.100) was used as the cut-off in patients with advanced melanoma. MALT1 levels at T were significantly increased in patients with advanced melanoma compared with in HCs (P<0.001). In patients with advanced melanoma, MALT1 was significantly decreased from T to T (P<0.001). Objective response rate (ORR) and disease control rate (DCR) were 28.6 and 59.2%, respectively. MALT1 levels at T were significantly negatively associated with overall therapeutic response (P=0.001), ORR (P=0.009) and DCR (P=0.004). MALT1 levels at T were significantly inversely associated with overall therapeutic response (P=0.021) and ORR (P=0.036). Moreover, MALT1 levels >3.100 at T (P=0.027) and T (P=0.045) were significantly associated with shorter progression-free survival (PFS), and MALT1 levels >3.100 at T were significantly associated with a poor overall survival (OS; P=0.022). Multivariate Cox regression analysis demonstrated that MALT1 levels at T (>3.100 vs. ≤3.100) were significantly associated with a poor PFS [hazard ratio (HR)=2.248; P=0.037], and MALT1 levels at T (>3.100 vs. ≤3.100) were significantly associated with a poor OS (HR=4.332; P=0.007). In conclusion, MALT1 levels are reduced following PD-1 treatment, and a high MALT1 level is associated with a poor therapeutic response and shorter survival in patients with advanced melanoma receiving PD-1 inhibitor monotherapy.
晚期黑色素瘤是一种侵袭性且危险的皮肤癌形式，程序性细胞死亡蛋白1（PD - 1）抑制剂是晚期黑色素瘤患者推荐的治疗选择。黏膜相关淋巴组织1（MALT1）会损害CD8 T细胞的激活，从而诱导免疫逃逸，导致PD - 1抑制剂的抗肿瘤效果降低。本研究旨在评估MALT1在接受PD - 1抑制剂单药治疗的晚期黑色素瘤患者中的预后意义。通过逆转录定量聚合酶链反应评估了20名健康对照者（HCs）入组后以及49例晚期黑色素瘤患者在接受PD - 1抑制剂单药治疗前（T0）、治疗2个月后（T2）和4个月后（T4）的血液MALT1水平。将HCs中MALT1的最高水平（3.100）用作晚期黑色素瘤患者的临界值。与HCs相比，晚期黑色素瘤患者在T0时的MALT1水平显著升高（P<0.001）。在晚期黑色素瘤患者中，MALT1从T0到T4显著降低（P<0.001）。客观缓解率（ORR）和疾病控制率（DCR）分别为28.6%和59.2%。T0时的MALT1水平与总体治疗反应（P = 0.001）、ORR（P = 0.009）和DCR（P = 0.004）显著负相关。T2时的MALT1水平与总体治疗反应（P = 0.021）和ORR（P = 0.036）显著负相关。此外，T0时MALT1水平>3.100（P = 0.027）和T2时MALT1水平>3.100（P = 0.045）与较短的无进展生存期（PFS）显著相关，T0时MALT1水平>3.100与较差的总生存期（OS；P = 0.022）显著相关。多因素Cox回归分析表明，T0时MALT1水平（>3.100 vs.≤3.100）与较差的PFS显著相关[风险比（HR）=2.248；P = 0.037]，T2时MALT1水平（>3.100 vs.≤3.100）与较差的OS显著相关（HR = 4.332；P = 0.007）。总之，PD - 1治疗后MALT1水平降低，在接受PD - 1抑制剂单药治疗的晚期黑色素瘤患者中，高MALT1水平与较差的治疗反应和较短的生存期相关。
