Abstract：
Immune checkpoint blockade therapy (ICB) is ineffective against cold tumors and, although it is effective against some hot tumors, drug resistance can occur. We have developed a Plasmodium immunotherapy (PI) that can overcome these shortcomings. However, the specific killing effect of PI on tumor cells is relatively weak. Radiotherapy (RT) is known to have strong specific lethality to tumor cells. Therefore, we hypothesized that PI combined with RT could produce synergistic antitumor effects. We tested our hypothesis using orthotopic and subcutaneous models of mouse glioma (GL261, a cold tumor) and a subcutaneous model of mouse non-small cell lung cancer (NSCLC, LLC, a hot tumor). Our results showed that, compared with each monotherapy, the combination therapy more significantly inhibited tumor growth and extended the life span of tumor-bearing mice. More importantly, the combination therapy could cure approximately 70 percent of glioma. By analyzing the immune profile of the tumor tissues, we found that the combination therapy was more effective in upregulating the perforin-expressing effector CD8+ T cells and downregulating the myeloid-derived suppressor cells (MDSCs), and was thus more effective in the treatment of cancer. The clinical transformation of PI combined with RT in the treatment of solid tumors, especially glioma, is worthy of expectation.
摘要：
免疫检查点阻断疗法(ICB)对冷肿瘤无效，尽管它对一些热肿瘤有效，可发生耐药性。我们开发了一种可以克服这些缺点的疟原虫免疫疗法（PI）。然而,PI对肿瘤细胞的特异性杀伤作用相对较弱。已知放射疗法(RT)对肿瘤细胞具有很强的特异性致死性。因此,我们假设PI联合RT可以产生协同抗肿瘤作用。我们使用小鼠神经胶质瘤（GL261，冷肿瘤）的原位和皮下模型和小鼠非小细胞肺癌（NSCLC，LLC,热肿瘤)。我们的研究结果表明,与每种单一疗法相比，联合治疗更明显地抑制肿瘤生长，延长荷瘤小鼠的寿命。更重要的是,联合治疗可以治愈大约70%的神经胶质瘤。通过分析肿瘤组织的免疫谱,我们发现联合疗法在上调表达穿孔素的效应CD8+T细胞和下调髓源性抑制细胞（MDSCs）方面更有效，因此在治疗癌症方面更有效。PI联合RT治疗实体肿瘤的临床转化，尤其是神经胶质瘤,值得期待。
