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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11268090PMC
http://dx.doi.org/10.3892/ol.2024.14566DOI Listing

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