Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Oxidative Stress as a Mediator of the Immunomodulation Exerted by Monoclonal Antibodies in the Treatment of Lung Cancer in Mice

Version 1 : Received: 7 June 2019 / Approved: 10 June 2019 / Online: 10 June 2019 (16:12:57 CEST)

A peer-reviewed article of this Preprint also exists.

Tang, J.; Ramis-Cabrer, D.; Wang, X.; Barreiro, E. Immunotherapy with Monoclonal Antibodies in Lung Cancer of Mice: Oxidative Stress and Other Biological Events. Cancers 2019, 11, 1301. Tang, J.; Ramis-Cabrer, D.; Wang, X.; Barreiro, E. Immunotherapy with Monoclonal Antibodies in Lung Cancer of Mice: Oxidative Stress and Other Biological Events. Cancers 2019, 11, 1301.

Abstract

Background: Lung cancer (LC) is a major leading cause of death worldwide. Immunomodulators that target several immune mechanisms have proven to reduce tumor burden in experimental models through induction of the immune microenvironment. We hypothesized that other biological mechanisms may also favor tumor burden reduction in lung cancer-bearing mice treated with immunomodulators. Methods: Tumor weight, area, and immune cells (T, B, macrophages, and TNF-alpha levels, immunohistochemistry) and tumor growth, oxidative stress, apoptosis, autophagy, and sirtuin-1 markers were analyzed (immunoblotting) in subcutaneous tumor of BALB/c mice injected with LP07 adenocarcinoma cells treated with monoclonal antibodies (CD-137, CTLA-4, PD-1, and CD-19, N=9/group) and non-treated control animals. Results: Compared to non-treated cancer mice, in tumors of monoclonal-treated animals, tumor area and weight and ki-67 significantly reduced, while T cell counts, oxidative stress, apoptosis, autophagy, and sirtuin-1 marker increased. Conclusion: Immunomodulators elicited a reduction in tumor burden (reduced tumor size and weight) through decreased tumor proliferation and increased oxidative stress, apoptosis, autophagy, and sirtuin-1 levels, which may have interfered with the immune profile of the tumor microenvironment. Future research should be devoted to the elucidation of the specific contribution of each biological mechanism to the reduced tumor burden.

Keywords

experimental lung cancer; immunomodulators; oxidative stress; autophagy; tumor growth; sirtuin-1

Subject

Medicine and Pharmacology, Oncology and Oncogenics

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