Phosphatases in Tumor Cell Immune Escape: A Perspective Based on the Camouflage, Coercion, Cytoprotection

Chencheng Zhang^1,2Shudong Zhu^1,2,3*

• ¹Nantong Tumor Hospital, Nantong, China
• ²Nantong University, Nantong, China
• ³Central South University, Changsha, China

Tumor immune evasion represents a core challenge restricting the efficacy of cancer treatment, and a deep understanding of its underlying mechanisms is crucial for developing novel immunotherapeutic approaches. This article focuses on the multidimensional regulatory roles of protein phosphatases in this critical biological process, innovatively adopting the "three Cs" framework—camouflage, coercion, and cytoprotection—for systematic elaboration, thereby revealing phosphatases as core molecular switches within dynamic regulatory networks. Our review systematically demonstrates that protein phosphatases serve as indispensable "dynamic molecular switches" within the "three Cs" framework of tumor immune evasion. Their regulatory networks span the entire continuum of tumor cells evading recognition, inhibiting immune cell function, and resisting terminal immune attacks. This insight underscores the substantial potential of targeting phosphatase regulatory networks, which may overcome the drug resistance bottleneck encountered in current immunotherapies. By designing novel drug strategies to precisely intervene in key phosphatase nodes—thereby achieving "one target, multiple effects" synergistic regulation—this framework provides a robust theoretical foundation and promising new avenues for developing more efficient, broad-spectrum next-generation tumor immunotherapies.