Immunotherapy with monoclonal antibodies in lung cancer of mice : oxidative stress and other biological events
Barreiro, Esther (Universitat Pompeu Fabra. Departament de Ciències Experimentals i de la Salut)
Tang, Jun (Universitat Autònoma de Barcelona. Departament de Medicina)
Ramis-Cabrer, Daniel. (Universitat Pompeu Fabra. Departament de Ciències Experimentals i de la Salut)
Wang, Xuejie (Universitat Autònoma de Barcelona. Departament de Medicina)

Data:	2019
Resum:	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, T cells and tumor growth (immunohistochemistry), oxidative stress, apoptosis, autophagy, and signaling (NF-κB 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 were significantly reduced, while T cell counts, oxidative stress, apoptosis, autophagy, activated p65, and sirtuin-1 markers were increased. Conclusions: Immunomodulators elicited a reduction in tumor burden (reduced tumor size and weight) through decreased tumor proliferation and increased oxidative stress, apoptosis, autophagy, and signaling markers, 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.
Ajuts:	Instituto de Salud Carlos III FIS/14-00713 Instituto de Salud Carlos III FIS/18-00075
Nota:	Altres ajuts: This study has been supported by CIBERES; SEPAR 2016; SEPAR 2018; FUCAP 2016; Unrestricted grant from Menarini SA 2018 (Spain), and GlaxoSmithKline SA (Spain) 2018.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Autophagy ; Experimental lung cancer ; Immunomodulators ; Oxidative stress ; Sirtuin-1 ; Tumor growth
Publicat a:	Cancers, Vol. 11 Núm. 9 (september 2019) , p. 1301, ISSN 2072-6694

DOI: 10.3390/cancers11091301
PMID: 31487876

16 p, 3.3 MB

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