KEY TAKEAWAYS
- The study aimed to assess the influence of MOMP activity on immune modulation in cancer therapeutics.
- The results revealed that the MOMP is correlated to immune modulation ; clinically validated in skin cutaneous melanoma.
Mitochondrial outer membrane permeabilisation (MOMP) has a crucial role to play in cell-death and immune activation. A deeper insights over the impact of tumour MOMP on immunity will assist in guiding more effective immunotherapeutic strategies across various types of cancers, the present study offers validation for the same in Melanoma.
Qingshan Chen and the team investigated the MOMP activity influence on clinical prognosis, immune infiltration, and the effectiveness of immunotherapy.
Researchers conducted a comprehensive pan-cancer analysis using a dataset comprising 30 cancer-type transcriptomic cohorts, 20 immunotherapy transcriptomic cohorts, and 3 immunotherapy scRNA-seq datasets was collected and analyzed.
The study investigated the impact of MOMP activity on immunotherapy outcomes using 65 scRNA-Seq datasets, the study developed a MOMP signature (MOMP.Sig) to accurately measure tumor MOMP activity.
Machine learning models were utilized to invade into the clinical predictive insights and evaluate the value of MOMP.Sig. Further, by integratng the MOMP.Sig model with a pan-cancer immunotherapy CRISPR screen identified potential targets for overcoming immunotherapy resistance, which were then clinically validated.
Results identified that enhanced MOMP activity correlated with reduced mortality risk among patients with cancer, which fostered an anti-tumor immune activity, and amplified responsiveness to immunotherapy. These insights advocated the potential clinical significance of MOMP activity in immunotherapeutic approaches.
The MOMP.Sig demonstrated exceptional predictive accuracy in machine-learning models and leveraging the MOMP.Sig model which revealed FOXO1 as a pivotal regulator that inclined immune resistance. Notably, these findings were validated in clinical cohorts of skin cutaneous melanoma and patients with triple-negative breast cancer undergoing immunotherapy.
The study advanced the understanding of the relevance of MOMP activity in the context of immune modulation, offering valuable insights to optimize immunotherapeutic strategies across various types of cancers.
The study was funded by Natural Science Foundation of China.
Source: https://pubmed.ncbi.nlm.nih.gov/38899748/
Chen Q., Gao F., Wu J., et al. (2024). “Comprehensive pan-cancer analysis of mitochondrial outer membrane permeabilisation activity reveals positive immunomodulation and assists in identifying potential therapeutic targets for immunotherapy resistance.” Clin Transl Med. 2024 Jun;14(6):e1735. doi: 10.1002/ctm2.1735. PMID: 38899748.
