Preclinical Study of Plasmodium Immunotherapy Combined with Radiotherapy for Solid Tumors

• Published in: Cells (Basel, Switzerland) Switzerland), 2022-11, Vol.11 (22), p.3600
• Main Authors: Tao, Zhu, Ding, Wenting, Cheng, Zhipeng, Feng, Yinfang, Kang, Zhongkui, Qiu, Runmin, Zhao, Siting, Hu, Wen, Zhou, Fang, Wu, Donghai, Duan, Ziyuan, Qin, Li, Chen, Xiaoping
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Antigens; Antitumor activity; antitumor immune response; Brain cancer; Brain research; Brain tumors; Carcinoma, Non-Small-Cell Lung; CD8 antigen; CD8-Positive T-Lymphocytes; Cell Line, Tumor; Clinical trials; Cold; Drug resistance; Effector cells; Glioma; Glioma - pathology; Glioma - therapy; Immune checkpoint; Immunotherapy; Immunotherapy - methods; Laboratory animals; Lethality; Life span; Lung cancer; Lung Neoplasms; Lymphocytes; Lymphocytes T; Metastasis; Mice; Non-small cell lung carcinoma; Perforin; Plasmodium; Plasmodium immunotherapy; Radiation therapy; radiotherapy; Signal transduction; Small cell lung carcinoma; Solid tumors; Suppressor cells; Tumor cells; Tumors
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells11223600

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 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.