Humanized PD-1 Knock-in Mice Reveal Nivolumab's Inhibitory Effects on Glioblastoma Tumor Progression

Overview

Journal In Vivo

Specialty Oncology

Date 2023 Aug 31

PMID 37652472

Authors

Chun-Yu Chiang

Meng-Chu Huang

Shih-Chong Tsai

Fei-Ting Hsu

Tsai-Lan Liao

Jei-Hwa Yu

Tzu-Hsiang Lin

Hua-Hsih Huang

Pen-An Liao

Affiliations

Soon will be listed here.

Abstract

Background/aim: Immunotherapy has been considered a promising approach for brain tumor treatment since the discovery of the brain lymphatic system. Glioblastoma (GBM), the most aggressive type of brain tumor, is associated with poor prognosis and a lack of effective treatment options.

Materials And Methods: To test the efficacy of human anti-PD-1, we used a humanized PD-1 knock-in mouse to establish an orthotopic GBM-bearing model.

Results: Nivolumab, a human anti-PD-1, effectively inhibited tumor growth, increased the survival rate of mice, enhanced the accumulation and function of cytotoxic T cells, reduced the accumulation and function of immunosuppressive cells and their related factors, and did not induce tissue damage or biochemical changes. The treatment also induced the accumulation and activation of CD8 cytotoxic T cells, while reducing the accumulation and activation of myeloid-derived suppressor cells, regulatory T cells, and tumor-associated macrophages in the immune microenvironment.

Conclusion: Nivolumab has the potential to be a treatment for GBM.

Citing Articles

Towards Effective Treatment of Glioblastoma: The Role of Combination Therapies and the Potential of Phytotherapy and Micotherapy.

Gaiaschi L, Bottone M, De Luca F Curr Issues Mol Biol. 2024; 46(12):14324-14350.

PMID: 39727987 PMC: 11674107. DOI: 10.3390/cimb46120859.

References

Chen Y, Chang Y, Wang K, Chen P, Hseu Y, Chen K . Naringenin inhibited migration and invasion of glioblastoma cells through multiple mechanisms. Environ Toxicol. 2018; 34(3):233-239. DOI: 10.1002/tox.22677. View

Xie Q, Ding J, Chen Y . Role of CD8 T lymphocyte cells: Interplay with stromal cells in tumor microenvironment. Acta Pharm Sin B. 2021; 11(6):1365-1378. PMC: 8245853. DOI: 10.1016/j.apsb.2021.03.027. View

Reardon D, Brandes A, Omuro A, Mulholland P, Lim M, Wick A . Effect of Nivolumab vs Bevacizumab in Patients With Recurrent Glioblastoma: The CheckMate 143 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020; 6(7):1003-1010. PMC: 7243167. DOI: 10.1001/jamaoncol.2020.1024. View

Vu S, Vetrivel P, Kim J, Lee M . Cancer Resistance to Immunotherapy: Molecular Mechanisms and Tackling Strategies. Int J Mol Sci. 2022; 23(18). PMC: 9513751. DOI: 10.3390/ijms231810906. View

Wachsberger P, Burd R, Cardi C, Thakur M, Daskalakis C, Holash J . VEGF trap in combination with radiotherapy improves tumor control in u87 glioblastoma. Int J Radiat Oncol Biol Phys. 2007; 67(5):1526-37. DOI: 10.1016/j.ijrobp.2006.11.011. View

Subramanian A, Tamayo P, Mootha V, Mukherjee S, Ebert B, Gillette M . Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005; 102(43):15545-50. PMC: 1239896. DOI: 10.1073/pnas.0506580102. View

Hu Y, Huang L, Zhao K, Li Y, Givens N, Heslin A . CTHRC1 Is Associated With Immune Escape and Poor Prognosis in Gastric Cancer. Anticancer Res. 2022; 43(1):115-126. DOI: 10.21873/anticanres.16140. View

Mauldin I, Jo J, Wages N, Yogendran L, Mahmutovic A, Young S . Proliferating CD8 T Cell Infiltrates Are Associated with Improved Survival in Glioblastoma. Cells. 2021; 10(12). PMC: 8699921. DOI: 10.3390/cells10123378. View

Hsu F, Tsai C, Chiang I, Lan K, Yueh P, Liang W . Synergistic effect of Abraxane that combines human IL15 fused with an albumin-binding domain on murine models of pancreatic ductal adenocarcinoma. J Cell Mol Med. 2022; 26(7):1955-1968. PMC: 8980892. DOI: 10.1111/jcmm.17220. View

10.

Yang X, Wang G, Song Y, Zhuang T, Li Y, Xie Y . PD-1CD8 T Cells Proximal to PD-L1CD68 Macrophages Are Associated with Poor Prognosis in Pancreatic Ductal Adenocarcinoma Patients. Cancers (Basel). 2023; 15(5). PMC: 10000394. DOI: 10.3390/cancers15051389. View

11.

Wang N, Jain R, Batchelor T . New Directions in Anti-Angiogenic Therapy for Glioblastoma. Neurotherapeutics. 2017; 14(2):321-332. PMC: 5398985. DOI: 10.1007/s13311-016-0510-y. View

12.

Takimoto Y, Tsubamoto H, Isono-Taniguchi R, Ueda T, Sakata K, Nakagawa K . Itraconazole Modulates Phospholipid Levels in Tumor-associated Macrophages. Anticancer Res. 2023; 43(5):1981-1984. DOI: 10.21873/anticanres.16358. View

13.

Boutilier A, Elsawa S . Macrophage Polarization States in the Tumor Microenvironment. Int J Mol Sci. 2021; 22(13). PMC: 8268869. DOI: 10.3390/ijms22136995. View

14.

Liu K, Sun Q, Liu Q, Li H, Zhang W, Sun C . Focus on immune checkpoint PD-1/PD-L1 pathway: New advances of polyphenol phytochemicals in tumor immunotherapy. Biomed Pharmacother. 2022; 154:113618. DOI: 10.1016/j.biopha.2022.113618. View

15.

Park J, Lee H, Choi J, Lim S, Koh H, Cho K . Clinical Benefit of Bevacizumab and Irinotecan (BEV+IRI) in Patients With Relapsed/Refractory Glioblastoma (r/rGBM) and its Potential Predictors. Anticancer Res. 2022; 42(12):6091-6098. DOI: 10.21873/anticanres.16121. View

16.

Hosseinalizadeh H, Mahmoodpour M, Razaghi Bahabadi Z, Hamblin M, Mirzaei H . Neutrophil mediated drug delivery for targeted glioblastoma therapy: A comprehensive review. Biomed Pharmacother. 2022; 156:113841. DOI: 10.1016/j.biopha.2022.113841. View

17.

Manukian G, Kivolowitz C, DeAngelis T, Shastri A, Savage J, Camphausen K . Caloric Restriction Impairs Regulatory T cells Within the Tumor Microenvironment After Radiation and Primes Effector T cells. Int J Radiat Oncol Biol Phys. 2021; 110(5):1341-1349. PMC: 8286289. DOI: 10.1016/j.ijrobp.2021.02.029. View

18.

Narita Y . Bevacizumab for glioblastoma. Ther Clin Risk Manag. 2015; 11:1759-65. PMC: 4671800. DOI: 10.2147/TCRM.S58289. View

19.

Hsu F, Liu Y, Tsai C, Yueh P, Chang C, Lan K . Preclinical Evaluation of Recombinant Human IL15 Protein Fused with Albumin Binding Domain on Anti-PD-L1 Immunotherapy Efficiency and Anti-Tumor Immunity in Colon Cancer and Melanoma. Cancers (Basel). 2021; 13(8). PMC: 8070266. DOI: 10.3390/cancers13081789. View

20.

Li Y, Yu J, Liu Z, Yang H, Tang J, Chen Z . Programmed Death Ligand 1 Indicates Pre-Existing Adaptive Immune Response by Tumor-Infiltrating CD8 T Cells in Non-Small Cell Lung Cancer. Int J Mol Sci. 2019; 20(20). PMC: 6829548. DOI: 10.3390/ijms20205138. View