キラーＴ細胞のエネルギー代謝機構の解析とＰＤ－１阻害がん免疫治療の効果予測

我们将无应答性原因分为：1)局部原因无应答；2)具有全身免疫抑制特性（SIP）的无应答性。此外，我们发现PD-1阻断后的免疫反应与线粒体激活有关。基于这一结果，我们得出结论，线粒体激活可以作为识别应答者和无应答者的生物标志物。此外，我们发现sip阳性肿瘤释放非蛋白小分子，抑制线粒体激活和T细胞增殖。当与培养上液一起使用时，贝扎贝特可以消除上液的抑制作用。与单独阻断PD-1相比，贝扎布拉特联合PD-1阻断治疗可提高sip阳性肿瘤宿主的生存率。

We classified unresponsiveness reasons into i). unresponsvieness because of local reasons ii). unresponsiveness because of having systemic immunosuppressive property (SIP). In addition, we found immune response after PD-1 blockade is associated with mitochondrial activation. Based on this result, we concluded that mitochondrial activation could be biomarker to identify responder and nonresponders. Further, we found SIP-positive tumors release non-proteinaceous small molecule that inhibit mitochondrial activation and proliferation of T cells. Bezafibrate when used alongwith culture superntant cancels the suppressive effect of supernatnat. Bezafibrate treatment alongwith PD-1 blockade enhances the survival of host bearing SIP-positive tumor compared to PD-1 blockade alone.