KEY TAKEAWAYS
- The study aimed to examine the correlation between METTL14 and PD-1 ICI in lung cancer.
- The results showed that METTL14 disruption enhanced CD8+ T-cell activation, improving PD-1 immunotherapy against lung cancer.
The significance of N6-methyladenosine (m6A) modification in lung cancer is well recognized. Yet, the involvement of methyltransferase-like 14 (METTL14), a key component of the m6A complex, in the immune microenvironment of lung cancer remains less explored.
Chongqi Sun and the team sought to examine the association between METTL14 and the programmed death receptor 1 (PD-1) immune checkpoint inhibitor in lung cancer.
The study conducted a series of assays, including CCK-8, colony formation, transwell, wound healing, and flow cytometry, to investigate METTL14’s role in lung cancer progression in vitro. Additionally, they treated syngeneic model mice with sh-METTL14 and an anti-PD-1 antibody to assess METTL14’s impact on immunotherapy.
Flow cytometry and immunohistochemical staining were utilized to measure CD8 expression. They employed RIP and MeRIP techniques to explore the relationship between METTL14 and HSD17B6. In vitro, coculturing of LLC cells and activated mouse PBMCs was conducted to simulate immune cell infiltration in the tumor microenvironment. ELISA was employed to measure IFN-γ and TNF-α levels.
The results revealed that according to the online database GEPIA, high METTL14 expression correlated with poor prognosis among lung cancer patients. In vitro assays indicated that suppressing METTL14 hindered lung cancer progression.
In vivo experiments demonstrated that METTL14 suppression impeded tumor growth and improved responsiveness to PD-1 immunotherapy. Moreover, METTL14 suppression augmented CD8+ T-cell activation and infiltration. Notably, METTL14 suppression increased HSD17B6 mRNA stability by reducing its m6A methylation. Additionally, overexpression of HSD17B6 facilitated CD8+ T-cell activation.
The study concluded that disrupting METTL14 enhanced CD8+ T-cell activation and improved the response to PD-1 immunotherapy in lung cancer. This was achieved by modifying HSD17B6 with m6A, ultimately suppressing cancer progression.
Funding was provided by the National Natural Science Foundation of China.
Source: https://pubmed.ncbi.nlm.nih.gov/38725005/
Sun C, Wang J, Li H, et al. (2024). “METTL14 regulates CD8+T-cell activation and immune responses to anti-PD-1 therapy in lung cancer.” World J Surg Oncol. 2024 May 10;22(1):128. doi: 10.1186/s12957-024-03402-9. PMID: 38725005.
