Plasmodium immunotherapy combined with gemcitabine has a synergistic inhibitory effect on tumor growth and metastasis in murine Lewis lung cancer models

作者全名："Chen, Xiao; Tao, Zhu; Liang, Yun; Ma, Meng; Adah, Dickson; Ding, Wenting; Chen, Lili; Li, Xiaofen; Dai, Linglin; Fanuel, Songwe; Zhao, Siting; Hu, Wen; Wu, Donghai; Duan, Ziyuan; Zhou, Fang; Qin, Li; Chen, Xiaoping; Yang, Zhaoqing"

作者地址："[Chen, Xiao] Kunming Med Univ, Affiliated Hosp 1, Dept Med Oncol, Kunming, Yunnan, Peoples R China; [Chen, Xiao; Tao, Zhu; Liang, Yun; Ma, Meng; Adah, Dickson; Chen, Lili; Li, Xiaofen; Dai, Linglin; Fanuel, Songwe; Zhao, Siting; Wu, Donghai; Duan, Ziyuan; Chen, Xiaoping] Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Ctr Infect & Immun, State Key Lab Resp Dis, Guangzhou, Guangdong, Peoples R China; [Tao, Zhu; Ding, Wenting; Zhao, Siting; Hu, Wen; Zhou, Fang; Qin, Li; Chen, Xiaoping] Chinese Acad Sci, Lamvac Guangzhou Biomed Technol Co Ltd, Guangzhou, Guangdong, Peoples R China; [Liang, Yun] Kunming Med Univ, Affiliated Hosp 1, Dept Hepatobiliary Surg, Kunming, Yunnan, Peoples R China; [Ma, Meng] Chongqing Med Univ, Coll Lab Med, Key Lab Lab Med Diagnost, Minist Educ, Chongqing, Peoples R China; [Fanuel, Songwe] Midlands State Univ, Fac Sci & Technol, Dept Appl Biosci & Biotechnol, Gweru, Zimbabwe; [Yang, Zhaoqing] Kunming Med Univ, Dept Pathogen Biol & Immunol, Kunming, Yunnan, Peoples R China"

通信作者："Chen, XP (通讯作者)，Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Ctr Infect & Immun, State Key Lab Resp Dis, Guangzhou, Guangdong, Peoples R China.; Qin, L; Chen, XP (通讯作者)，Chinese Acad Sci, Lamvac Guangzhou Biomed Technol Co Ltd, Guangzhou, Guangdong, Peoples R China.; Yang, ZQ (通讯作者)，Kunming Med Univ, Dept Pathogen Biol & Immunol, Kunming, Yunnan, Peoples R China."

来源：FRONTIERS IN ONCOLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001093392400001

JCR分区：Q2

影响因子：3.5

年份：2023

卷号：13

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Plasmodium immunotherapy; Plasmodium chabaudi ASS; gemcitabine; anticancer effect; synergism; mouse lung cancer model

摘要："Objective: Our previous studies have demonstrated that Plasmodium immunotherapy (infection) has antitumor effects in mice. However, as a new form of immunotherapy, this therapy has a weakness: its specific killing effect on tumor cells is relatively weak. Therefore, we tested whether Plasmodium immunotherapy combined with gemcitabine (Gem), a representative chemotherapy drug, has synergistic antitumor effects.Methods: We designed subcutaneously and intravenously implanted murine Lewis lung cancer (LLC) models to test the antitumor effect of Plasmodium chabaudi ASS (Pc) infection in combination with Gem treatment and explored its underlying mechanisms.Results: We found that both Pc infection alone and Gem treatment alone significantly inhibited tumor growth in the subcutaneous model, and combination therapy was more effective than either monotherapy. Monotherapy only tended to prolong the survival of tumor-bearing mice, while the combination therapy significantly extended the survival of mice, indicating a significant synergistic effect of the combination. In the mechanistic experiments, we found that the combination therapy significantly upregulated E-cadherin and downregulated Snail protein expression levels, thus inhibiting epithelial-mesenchymal transition (EMT) of tumor cells, which may be due to the blockade of CXCR2/TGF-beta-mediated PI3K/Akt/GSK-3 beta signaling pathway.Conclusion: The combination of Pc and Gem plays a synergistic role in inhibiting tumor growth and metastasis, and prolonging mice survival in murine lung cancer models. These effects are partially attributed to the inhibition of EMT of tumor cells, which is potentially due to the blockade of CXCR2/TGF-beta-mediated PI3K/Akt/GSK-3 beta/Snail signaling pathway. The clinical transformation of Plasmodium immunotherapy combined with Gem for lung cancer is worthy of expectation."

基金机构："This work was supported by grants from the Open Project of the State Key Laboratory Respiratory Disease (grant number: SKLRD-OP-201802), Program Grant of Guangzhou Innovation Leading Team in Sciences and Technologies (grant number: 201909010007) and the Ap [SKLRD-OP-201802]; Open Project of the State Key Laboratory Respiratory Disease [201909010007]; Program Grant of Guangzhou Innovation Leading Team in Sciences and Technologies [202101AY070001-084]; Applied Basic Research Projects of Yunnan Province"

基金资助正文："This work was supported by grants from the Open Project of the State Key Laboratory Respiratory Disease (grant number: SKLRD-OP-201802), Program Grant of Guangzhou Innovation Leading Team in Sciences and Technologies (grant number: 201909010007) and the Applied Basic Research Projects of Yunnan Province (grant number: 202101AY070001-084)."