Neogambogic acid enhances anti-PD-1 immunotherapy efficacy by attenuating suppressive function of MDSCs in pancreatic cancer

被引:0
作者
Xun, Jing [1 ,2 ,3 ]
Jiang, Xiaolin [1 ,2 ,3 ]
Liu, Bin [1 ,2 ,3 ]
Hu, Zhibo [1 ,2 ,3 ]
Liu, Jinjin [2 ,3 ,4 ]
Han, Yingdi [1 ,2 ,3 ]
Gao, Ruifang [5 ]
Zhang, Hui [2 ,3 ,4 ]
Yang, Shimin [1 ]
Yu, Xiangyang [1 ]
Wang, Ximo [1 ,2 ]
Yan, Chen [1 ,6 ]
Zhang, Qi [1 ,2 ,3 ]
机构
[1] Tianjin Med Univ, Tianjin Nankai Hosp, Tianjin 300100, Peoples R China
[2] Tianjin Key Lab Acute Abdomen Dis Associated Organ, Tianjin 300100, Peoples R China
[3] Inst Integrat Med Acute Abdominal Dis, Tianjin 300100, Peoples R China
[4] Tianjin Univ, Integrated Chinese & Western Med Hosp, Tianjin, Peoples R China
[5] Tianjin Inst Med & Pharmaceut Sci, Tianjin 300020, Peoples R China
[6] Tianjin Vocat Coll Bioengn, Tianjin 300301, Peoples R China
关键词
Pancreatic cancer; Neogambogic acid; Myeloid-derived suppressor cells (MDSCs); Anti-PD-1; antibody; Immunotherapy; GAMBOGIC ACID; CELLS; NANOPARTICLES; APOPTOSIS; DELETION;
D O I
10.1016/j.intimp.2024.112696
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background: Anti-PD-1-based immunotherapy has limited benefits in patients with pancreatic cancer. Accumulating data indicate that natural products exert antitumor activity by remodeling the tumor immune microenvironment. It has been reported that neogambogic acid (NGA), an active natural monomer extracted from Garcinia, has anti-inflammatory and antitumor effects. Nevertheless, there are few systematic studies on the antitumor efficacy and immunomodulatory effects of NGA in pancreatic cancer. Methods: An orthotopic mouse model of pancreatic cancer was established and were treated with different doses of NGA. Tumor growth and ascites were observed. Flow cytometry and immunohistochemistry (IHC) were used to investigate the tumor immune microenvironment. CD11b+ MDSCs were infused back into mice with pancreatic cancer to observe tumor progression after NGA treatment. Bone marrow cells were induced to differentiate into MDSCs, and the effects of NGA on MDSCs were analyzed and the underlying mechanism was explored. The effects of NGA combined with an anti-PD-1 antibody on pancreatic cancer were further tested. Results: NGA significantly inhibited the tumor growth and improve ascites character in pancreatic cancer model mice. Flow cytometry and IHC analysis revealed that NGA decreased the MDSCs proportion and infiltration in the tumor microenvironment. Moreover, adoptive MDSCs largely attenuated the inhibitory effect of NGA on the progression of pancreatic cancer. In addition, we showed that NGA significantly promoted apoptosis and inhibited the differentiation, migration and immunosuppressive function of MDSCs and decreased level of STAT3 and p-STAT3. Furthermore, we demonstrated that NGA synergistically enhanced the efficacy of anti-PD-1 antibodies against pancreatic cancer. Conclusion: NGA inhibited the progression of pancreatic cancer by inhibiting MDSCs in the tumor microenvironment, and enhanced the efficacy of anti-PD-1 therapy in the treatment of pancreatic cancer.
引用
收藏
页数:13
相关论文
共 50 条
  • [31] Efficacy and safety of anti-PD-1 and anti-PD-1 combined with anti-CTLA-4 immunotherapy to advanced melanoma: A systematic review and meta-analysis of randomized controlled trials
    Hao, Chunyan
    Tian, Jinhui
    Liu, Huiling
    Li, Fei
    Niu, Hongxia
    Zhu, Bingdong
    MEDICINE, 2017, 96 (26)
  • [32] Targeting cancer-associated adipocyte-derived CXCL8 inhibits triple-negative breast cancer progression and enhances the efficacy of anti-PD-1 immunotherapy
    Huang, Renhong
    Wang, Zheng
    Hong, Jin
    Wu, Jiayi
    Huang, Ou
    He, Jianrong
    Chen, Weiguo
    Li, Yafen
    Chen, Xiaosong
    Shen, Kunwei
    CELL DEATH & DISEASE, 2023, 14 (10)
  • [33] ARID1A alterations function as a biomarker for longer progression-free survival after anti-PD-1/PD-L1 immunotherapy
    Okamura, Ryosuke
    Kato, Shumei
    Lee, Suzanna
    Jimenez, Rebecca E.
    Sicklick, Jason K.
    Kurzrock, Razelle
    JOURNAL FOR IMMUNOTHERAPY OF CANCER, 2020, 8 (01)
  • [34] Peripheral changes in T cells predict efficacy of anti-PD-1 immunotherapy in non-small cell lung cancer
    Lao, Juanfeng
    Xu, Huiting
    Liang, Zibin
    Luo, Changliang
    Shu, Liuyang
    Xie, Yuping
    Wu, Yongjian
    Hao, Yanrong
    Yuan, Yulin
    IMMUNOBIOLOGY, 2023, 228 (03)
  • [35] Targeting interferon signaling and CTLA-4 enhance the therapeutic efficacy of anti-PD-1 immunotherapy in preclinical model of HPV+ oral cancer
    Dorta-Estremera, Stephanie
    Hegde, Venkatesh L.
    Slay, Ravaen B.
    Sun, Rachel
    Yanamandra, Ananta, V
    Nicholas, Courtney
    Nookala, Sita
    Sierra, Gloria
    Curran, Michael A.
    Sastry, K. Jagannadha
    JOURNAL FOR IMMUNOTHERAPY OF CANCER, 2019, 7 (01)
  • [36] Anti-PD-1 antibody significantly increases therapeutic efficacy of Listeria monocytogenes (Lm)-LLO immunotherapy
    Mkrtichyan, Mikayel
    Chong, Namju
    Abu Eid, Rasha
    Wallecha, Anu
    Singh, Reshma
    Rothman, John
    Khleif, Samir N.
    JOURNAL FOR IMMUNOTHERAPY OF CANCER, 2013, 1
  • [37] Autophagy Blockage Up-Regulates HLA-Class-I Molecule Expression in Lung Cancer and Enhances Anti-PD-L1 Immunotherapy Efficacy
    Xanthopoulou, Erasmia
    Lamprou, Ioannis
    Mitrakas, Achilleas G.
    Michos, Georgios D.
    Zois, Christos E.
    Giatromanolaki, Alexandra
    Harris, Adrian L.
    Koukourakis, Michael I.
    CANCERS, 2024, 16 (19)
  • [38] Bifidobacterium breve predicts the efficacy of anti-PD-1 immunotherapy combined with chemotherapy in Chinese NSCLC patients
    Zhao, Honghui
    Li, Dan
    Liu, Jiayin
    Zhou, Xinliang
    Han, Jing
    Wang, Long
    Fan, Zhisong
    Feng, Li
    Zuo, Jing
    Wang, Yudong
    CANCER MEDICINE, 2023, 12 (05): : 6325 - 6336
  • [39] Systematic investigation of chemo-immunotherapy synergism to shift anti-PD-1 resistance in cancer
    Wang, Yue
    Pattarayan, Dhamotharan
    Huang, Haozhe
    Zhao, Yueshan
    Li, Sihan
    Wang, Yifei
    Zhang, Min
    Li, Song
    Yang, Da
    NATURE COMMUNICATIONS, 2024, 15 (01)
  • [40] Apatinib remodels the immunosuppressive tumor ecosystem of gastric cancer enhancing anti-PD-1 immunotherapy
    Luo, Qicong
    Dong, Zinan
    Xie, Wen
    Fu, Xiaoteng
    Lin, Lingyun
    Zeng, Qiang
    Chen, Yinggang
    Ye, Guodong
    Chen, Maoli
    Hu, Huiyu
    Wang, Lin
    Xie, Yuanyuan
    Cai, Wangyu
    CELL REPORTS, 2023, 42 (05):