Potential Treatment Approaches for Malignant Peritoneal Mesothelioma: in Vivo and in Vitro Experimental Study of Natural Killer Cell Immunotherapy

Overview

Journal Cancer Biol Med

Specialty Oncology

Date 2024 Nov 1

PMID 39485065

Authors

Heliang Wu

Yi Wang

Yulin Lin

Ru Ma

Xuemei Du

Yandong Su

Rui Yang

Zhiran Yang

Xinli Liang

Yinguang Zhang

Xiaoqing Liang

Zhonghe Ji

Chunning Lai

Yajing Huang

Yan Li

Affiliations

Soon will be listed here.

Abstract

Objective: Malignant peritoneal mesothelioma (MPM) is a rare primary malignant tumor with an extremely poor prognosis that currently lacks effective treatment options. This study investigated the and efficacy of natural killer (NK) cells for treatment of MPM.

Methods: An study was conducted to assess the cytotoxicity of NK cells from umbilical cord blood to MPM cells with the use of a high-content imaging analysis system, the Cell Counting Kit-8 assay, and Wright-Giemsa staining. The level of NK cell effector molecule expression was detected by flow cytometry and enzyme-linked immunosorbent assays. The ability of NK cells to kill MPM cells was determined based on live cell imaging, transmission electron microscopy, and scanning electron microscopy. An study was conducted to assess the efficacy and safety of NK cell therapy based on the experimental peritoneal cancer index, small animal magnetic resonance imaging, and conventional histopathologic, cytologic, and hematologic studies.

Results: NK cells effectively killed MPM cells through the release of effector molecules (granzyme B, perforin, interferon-γ, and tumor necrosis factor-α) in a dose- and density-dependent manner. The NK cell killing process potentially involved four dynamic steps: chemotaxis; hitting; adhesion; and penetration. NK cells significantly reduced the tumor burden, diminished ascites production, and extended survival with no significant hematologic toxicity or organ damage in NOG mice.

Conclusions: NK cell immunotherapy inhibited proliferation of MPM cells and with a good safety profile.

References

Sharma P, Hu-Lieskovan S, Wargo J, Ribas A . Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy. Cell. 2017; 168(4):707-723. PMC: 5391692. DOI: 10.1016/j.cell.2017.01.017. View

Vahedi F, Nham T, Poznanski S, Chew M, Shenouda M, Lee D . Ex Vivo Expanded Human NK Cells Survive and Proliferate in Humanized Mice with Autologous Human Immune Cells. Sci Rep. 2017; 7(1):12083. PMC: 5608690. DOI: 10.1038/s41598-017-12223-8. View

Wu H, Yang Z, Su Y, Ma R, Du X, Gao Y . Loss of NPM2 expression is a potential immunohistochemical marker for malignant peritoneal mesothelioma: a single-center study of 92 cases. World J Surg Oncol. 2022; 20(1):350. PMC: 9590226. DOI: 10.1186/s12957-022-02811-y. View

Cao B, Liu M, Huang J, Zhou J, Li J, Lian H . Development of mesothelin-specific CAR NK-92 cells for the treatment of gastric cancer. Int J Biol Sci. 2021; 17(14):3850-3861. PMC: 8495380. DOI: 10.7150/ijbs.64630. View

Marin N, Krasnick B, Becker-Hapak M, Conant L, Goedegebuure S, Berrien-Elliott M . Memory-like Differentiation Enhances NK Cell Responses to Melanoma. Clin Cancer Res. 2021; 27(17):4859-4869. PMC: 8416927. DOI: 10.1158/1078-0432.CCR-21-0851. View

Sung H, Ferlay J, Siegel R, Laversanne M, Soerjomataram I, Jemal A . Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3):209-249. DOI: 10.3322/caac.21660. View

Xiao J, Zhang T, Gao F, Zhou Z, Shu G, Zou Y . Natural Killer Cells: A Promising Kit in the Adoptive Cell Therapy Toolbox. Cancers (Basel). 2022; 14(22). PMC: 9688567. DOI: 10.3390/cancers14225657. View

Su Y, Yang Z, Li X, Yu Y, Du X, Li Y . Key factors for successful cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy to treat diffuse malignant peritoneal mesothelioma: results from specialized peritoneal cancer center in China. Int J Hyperthermia. 2022; 39(1):706-712. DOI: 10.1080/02656736.2022.2066728. View

Li C, Alexander Jr H . Peritoneal Metastases from Malignant Mesothelioma. Surg Oncol Clin N Am. 2018; 27(3):539-549. DOI: 10.1016/j.soc.2018.02.010. View

10.

Kusamura S, Kepenekian V, Villeneuve L, Lurvink R, Govaerts K, de Hingh I . Peritoneal mesothelioma: PSOGI/EURACAN clinical practice guidelines for diagnosis, treatment and follow-up. Eur J Surg Oncol. 2020; 47(1):36-59. DOI: 10.1016/j.ejso.2020.02.011. View

11.

Klapdor R, Wang S, Morgan M, Dork T, Hacker U, Hillemanns P . Characterization of a Novel Third-Generation Anti-CD24-CAR against Ovarian Cancer. Int J Mol Sci. 2019; 20(3). PMC: 6387114. DOI: 10.3390/ijms20030660. View

12.

Zhang Q, Zhang H, Ding J, Liu H, Li H, Li H . Combination Therapy with EpCAM-CAR-NK-92 Cells and Regorafenib against Human Colorectal Cancer Models. J Immunol Res. 2018; 2018:4263520. PMC: 6205314. DOI: 10.1155/2018/4263520. View

13.

Baghery Saghchy Khorasani A, Yousefi A, Bashash D . CAR NK cell therapy in hematologic malignancies and solid tumors; obstacles and strategies to overcome the challenges. Int Immunopharmacol. 2022; 110:109041. DOI: 10.1016/j.intimp.2022.109041. View

14.

Lee Y, Ju A, Choi H, Kim J, Kim E, Kim T . Rationally designed redirection of natural killer cells anchoring a cytotoxic ligand for pancreatic cancer treatment. J Control Release. 2020; 326:310-323. DOI: 10.1016/j.jconrel.2020.07.016. View

15.

Hoogstad-van Evert J, Cany J, van den Brand D, Oudenampsen M, Brock R, Torensma R . Umbilical cord blood CD34 progenitor-derived NK cells efficiently kill ovarian cancer spheroids and intraperitoneal tumors in NOD/SCID/IL2Rg mice. Oncoimmunology. 2017; 6(8):e1320630. PMC: 5593716. DOI: 10.1080/2162402X.2017.1320630. View

16.

McGranahan N, Swanton C . Clonal Heterogeneity and Tumor Evolution: Past, Present, and the Future. Cell. 2017; 168(4):613-628. DOI: 10.1016/j.cell.2017.01.018. View

17.

Ren C, Li M, Zheng Y, Cai B, Du W, Zhang H . Single-cell RNA-seq reveals altered NK cell subsets and reduced levels of cytotoxic molecules in patients with ankylosing spondylitis. J Cell Mol Med. 2022; 26(4):1071-1082. PMC: 8831943. DOI: 10.1111/jcmm.17159. View

18.

Chen M, Li Y, Wu Y, Xie S, Ma J, Yue J . Anti-Tumor Activity of Expanded PBMC-Derived NK Cells by Feeder-Free Protocol in Ovarian Cancer. Cancers (Basel). 2021; 13(22). PMC: 8616155. DOI: 10.3390/cancers13225866. View

19.

Huang J, Chan S, Pang W, Chow S, Lok V, Zhang L . Global Incidence, Risk Factors, and Temporal Trends of Mesothelioma: A Population-Based Study. J Thorac Oncol. 2023; 18(6):792-802. DOI: 10.1016/j.jtho.2023.01.095. View

20.

Su Y, Huang H, Luo T, Zheng Y, Fan J, Ren H . Cell-in-cell structure mediates in-cell killing suppressed by CD44. Cell Discov. 2022; 8(1):35. PMC: 9016064. DOI: 10.1038/s41421-022-00387-1. View