Marchf8, also known as membrane-associated ring-CH-type finger 8, is an E3 ubiquitin ligase. It plays a crucial role in multiple biological processes by regulating the ubiquitination and degradation of various proteins. It is involved in pathways such as selective autophagy, apoptosis regulation, and immune-related processes, which are vital for maintaining cellular homeostasis and the body's defense mechanisms [1,2,3,4]. Genetic models, especially gene knockout models, are valuable tools for studying its functions.

In HPV-positive head and neck cancer cells, knockdown of MARCHF8 restores the cell-surface expression of TNFRSF death receptors, enhances apoptosis, and in mouse oral cancer cells expressing HPV16 E6 and E7, MARCHF8 knockout augments cancer cell apoptosis and suppresses tumor growth in vivo, indicating its role in apoptosis regulation and cancer development [2]. In HPV-positive head and neck cancer, MARCHF8 knockdown also restores MHC-I levels on cells, and Marchf8 knockout in mice significantly suppresses tumor growth, increases the infiltration of natural killer and T cells in the tumor microenvironment, and enhances the tumor-cell-killing activity of CD8 + T cells. Additionally, Marchf8 knockout combined with anti-PD-1 treatment synergistically suppresses tumor growth in mice bearing ICI-refractory tumors, suggesting its potential as a target for immunotherapy in HPV-positive head and neck cancer patients [5].

In conclusion, Marchf8 is an important E3 ubiquitin ligase involved in diverse biological functions, especially in apoptosis regulation and cancer immune evasion. The study of Marchf8 knockout mouse models has provided significant insights into its role in HPV-related head and neck cancer, offering potential new strategies for cancer treatment.