Core Insights - Prostate cancer is the second most common malignant tumor in men globally, characterized by treatment resistance and high recurrence risk, presenting significant challenges for therapy [2] - Immune therapy has shown significant clinical benefits in various solid tumors, but its efficacy in "cold" tumors like prostate cancer remains limited, necessitating strategies to activate immune responses [2] - A recent study published in PNAS reveals that PSAT1 drives a feedback loop that enables prostate cancer cells to evade NK cell immune surveillance, providing new molecular targets and intervention strategies for treating "cold" tumors [2][10] Group 1: Research Findings - The research team found that PSAT1 is significantly overexpressed in prostate cancer tissues and correlates with poor patient prognosis, while its expression is negatively associated with the infiltration of key immune effector cells, particularly NK cells [4] - PSAT1 regulates immune evasion by enhancing the phosphorylation of YBX1, which subsequently increases PSAT1 transcription, forming a stable positive feedback loop [4] - YBX1, upon entering the nucleus, activates the expression of HLA-E, an inhibitory ligand for NK cells, leading to NK cell dysfunction and preventing their ability to kill prostate cancer cells [5] Group 2: Clinical Implications - In vitro and in vivo experiments demonstrated that targeting or inhibiting PSAT1 significantly reduces the immune evasion capability of prostate cancer cells, enhancing NK cell-mediated tumor cell killing and effectively suppressing tumor growth [6] - The combination of PSAT1 knockdown and NK cell infusion shows synergistic effects in inhibiting tumor growth, highlighting the therapeutic potential of disrupting this immune evasion pathway [6] Group 3: Future Directions - The study suggests that targeting the PSAT1-YBX1-HLA-E pathway could convert "cold" tumors into "hot" tumors that are more responsive to NK cell immunotherapy, opening new avenues for treatment [10] - Preliminary data indicate that this mechanism may also be present in other malignancies with high HLA-E expression, such as lung cancer and glioma, suggesting broader therapeutic potential [10]