Core Viewpoint - The study identifies PILRα as a potential immune checkpoint in cancer immunotherapy, which interacts with T cell surface protein CD99 to suppress anti-tumor immunity, indicating its clinical significance in various human cancers with poor prognosis [2][4][5]. Group 1 - The research published in Nature Cancer reveals that PILRα expressed on tumor cells inhibits T cell activation, proliferation, and effector functions by targeting CD99, affecting the ZAP70/NFAT/IL-2/JAK/STAT signaling pathway [3]. - Blocking the interaction between PILRα and CD99 using specific antibodies significantly enhances T cell anti-tumor immune responses and suppresses tumor growth, showing synergistic effects when combined with anti-PD-1 antibodies [3][5]. - High expression of PILRα in various human cancers is associated with unfavorable prognosis, highlighting its potential as a therapeutic target in cancer treatment [4].