Related Experiment Video
Updated: Jul 20, 2025
Analysis of Lymph Node Volume by Ultra-High-Frequency Ultrasound Imaging in the Braf/Pten Genetically Engineered Mouse Model of Melanoma
Published on: September 8, 2021
SETBP1 mutation determines sensitivity to immune checkpoint inhibitors in melanoma and NSCLC
Fengxiao An1, Wenjing Zhang2, Yuxian Guo2
1Department of Clinical Laboratory, Affiliated Hospital of Weifang Medical University, Weifang 261031, Shandong, China.
Abstract:
SET binding protein 1 (SETBP1) plays crucial roles in various biological processes; however, its involvement in cancer immune checkpoint inhibitor (ICI) treatments has never been studied. In this study, we collected a total of 631 melanoma and 109 non-small cell lung cancer (NSCLC) samples treated with ICI agents (i.e., anti-CTLA-4, anti-PD-1/PD-L1, or combination therapy). Additionally, we obtained their corresponding somatic mutational profiles. We observed that SETBP1 mutated (SETBP1-MUT) melanoma patients exhibited significantly prolonged ICI survival outcomes compared to wild-type patients (HR: 0.56, 95% CI: 0.38-0.81, P = 0.002). Consistently, an elevated ICI response rate was also noticed in the SETBP1-MUT group (42.9% vs. 29.1%, P = 0.016). The Association of SETBP1 mutations with favorable immunotherapeutic prognosis and response was further supported by an independent NSCLC cohort (both P < 0.05). Additional immunological analyses revealed that favorable immune infiltration, tumor immunogenicity, and immune response circuits were enriched in SETBP1-MUT patients. Overall, our findings suggest that SETBP1 mutations may serve as a new biomarker for stratifying beneficiaries of ICI treatments in melanoma and NSCLC, which provides possible evidence for tailoring clinical immunotherapeutic strategies.
Insights
SETBP1 mutations are linked to better outcomes in melanoma and non-small cell lung cancer patients receiving immune checkpoint inhibitors (ICIs). This suggests SETBP1 mutations could predict response to ICI therapy.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- SET binding protein 1 (SETBP1) has known biological roles, but its impact on cancer immunotherapy is unexplored.
- Immune checkpoint inhibitors (ICIs) like anti-CTLA-4 and anti-PD-1/PD-L1 are vital cancer treatments.
Purpose of the Study:
- To investigate the association between SETBP1 mutations and patient outcomes in melanoma and non-small cell lung cancer (NSCLC) treated with ICIs.
- To explore the immunological landscape in SETBP1-mutated tumors.
Main Methods:
- Analysis of somatic mutational profiles and clinical data from 631 melanoma and 109 NSCLC patients treated with ICIs.
- Comparison of survival outcomes and response rates between SETBP1-mutated and wild-type patients.
- Immunological analyses to assess immune infiltration, tumor immunogenicity, and immune response circuits.
Main Results:
- SETBP1-mutated melanoma patients showed significantly longer survival (HR: 0.56, P=0.002) and higher response rates (42.9% vs 29.1%, P=0.016) to ICIs.
- These favorable outcomes associated with SETBP1 mutations were confirmed in an independent NSCLC cohort.
- SETBP1-mutated tumors exhibited enriched immune infiltration, higher tumor immunogenicity, and enhanced immune response circuits.
Conclusions:
- SETBP1 mutations are associated with improved prognosis and response to ICI therapy in melanoma and NSCLC.
- SETBP1 mutations may serve as a predictive biomarker for stratifying patients likely to benefit from ICIs.
- These findings support the potential for tailoring clinical immunotherapeutic strategies based on SETBP1 mutation status.
