Negative impact of high body mass index on cetuximab-mediated cellular cytotoxicity against human colon carcinoma cells

Abstract

This study assessed the relationship between the ability of Natural Killer (NK) cells to activate antibody-dependent cellular cytotoxicity against human HT29 colorectal cancer cells exposed to cetuximab and the body mass index of the human subjects from whom the NK cells had been obtained. NK cells obtained from 73 human donors were co-incubated with HT-29 human colon cancer cells in the presence or absence of cetuximab. Antibody-dependent cellular cytotoxicity was assessed by measuring LDH release. A significant negative correlation was observed between body mass index and cetuximab-induced antibody-dependent cellular cytotoxicity. NK cells obtained from subjects who were overweight or with obesity were less efficient in killing cetuximab-treated HT29 cells than those derived from normal weight donors. Our results suggest that the success of cetuximab-containing regimens might be impaired in overweight and obese patients with colorectal cancer.

Keywords:

• Cetuximab
• colon cancer
• colon cancer cells
• Body Mass Index
• obesity
• citotoxicity

Disclosure statement

None of the Authors have any potential conflict of interest associated with this research.

Additional information

Funding

This study was supported by the Università degli Studi dell’Insubria, Fondi di Ateneo per la Ricerca (FAR) 2017 (to LC); FAR 2018 and Fondo Finanziamento per le Attività Base di Ricerca (FFABR) 2017 (to LM). The funding agencies were not involved in the research plan and the interpretation of the data.

Notes on contributors

Leonardo Campiotti

Dr. Leonardo Campiotti, MD, Assistent Professor of Internal Medicine, University of Insubria. Main interests in hemathology, oncology and immunotherapy.

Marzia Bruna Gariboldi

Prof. Marzia Bruna Gariboldi, PhD, Professor of Applied Biology. Author of research studies on anticancer pharmacology, photodynamic therapy, drug delivery systems, natural compounds as anticancer drugs, drug resistance.

Lorenzo Mortara

Prof. Lorenzo Mortara, PhD, Professor of General Pathology and Immunology. He has conducted research in tumor immunology, anti-viral immune responses and vaccines.

Douglas McClain Noonan

Prof. Douglas Noonan, PhD, Professor of General Pathology and Immunology. He has conducted research in the tumor microenvironment (extracellular matrix, angiogenesis, immune cells), author of more than 200 articles in peer-reviewed journals.

Daniela Gallo

Dr. Daniela Gallo, PhD in Experimental and Translational Medicine, involved in researches on obesity and thyroid autoimmune disorders.

Olga Nigro

Dr. Olga Nigro, MD, resident in Medical Oncology. Main interests in immunotherapy, tumor microenvironment, NSCLC and Melanoma.

Elena Monti

Prof. Eliana Piantanida, Associate Professor of Endocrinology, author of research studies mainly in the field of obesity and thyroid autoimmunity.