Study Describes a Casual Link Between Obesity and Cancer

A recent study shows a link between obesity and cancer. The study, published in journal Obesity, suggests that inflammatory cells that possess immunosuppressive properties may act as pivotal link between obesity and cancer risk, progression, and metastasis.

In this study, researchers conducted a literature review. Subsequently, they delineated altered metabolic factors of obesity such as lipids, insulin, and leptin. These factors, the researchers noted, contribute to the activation of immunosuppressive and cancer developing capabilities of myeloid cells.

“Deciphering the molecular mechanisms by which obesity-associated metabolic factors activate or enhance the function of Myeloid-derived Suppressor Cells and immunosuppressive macrophages will allow us to identify biomarkers for prognosis and therapeutic responses,” said Maria D. Sanchez-Pino, PhD, an assistant research professor in the departments of Interdisciplinary Oncology and Genetics at LSU Health New Orleans’ School of Medicine and Stanley S. Scott Cancer Center via a press release. “It will also lead to the discovery of potential targets for pharmacological therapies that may disrupt the pathophysiologic inflammatory link between obesity and cancer.”

“There is compelling evidence linking obesity to cancer; however, the underlying molecular mechanisms driving this association remain incompletely established. One of the major factors associated with the metabolic inflammation of obesity is the expansion of myeloid cells with immunosuppressive and pro-oncogenic abilities. Obesity is a complex disease with a malfunction of multiple factors that independently, or in combination, lead to the accumulation of myeloid cells. Although it is partly defined, several alterations that promote low-grade inflammation and expansion of myeloid immunosuppressive cells may include (i) nutrient oversupply, (ii) tissue hypoxia, (iii) excess of growth factors, cytokines, and lipolysis, and (iv) metabolic and endocrine abnormalities, such as dyslipidemia, deregulated signaling by insulin and leptin, altered levels of resistin and adiponectin, elevated bioavailable estrogen, and hypovitaminosis owing to sequestration of fat-soluble vitamins such as the immunomodulator vitamin D in body fat depots. All together, these factors may create the milieu for obesity-induced trained immunity,” the researchers concluded.

 

Important Questions Moving Forward

As research continues, the researchers noted, there are several outstanding questions to be considered. Some of these questions include:

  1. Is the elevated cancer risk in obesity due to the reprogramming of immune cells by systemic metabolic abnormalities? If so, the researchers wonder, do patients with obesity without metabolic syndrome have less accumulation of myeloid immunosuppressive cells and therefore a reduced risk of cancer?
  2. As some data demonstrate that patients who have had bariatric surgery have less chance of developing cancer, and cancer mortality, does bariatric surgery lower the risk of cancer by reversing the accumulation or function of immunosuppressive myeloid cells in patients with obesity?
  3. “Following our hypothesis that the risk of cancer is driven by the expansion and function of myeloid immunosuppressive cells in obesity, could the use of drugs known to target MDSCs and TAMs prevent cancer initiation in patients with morbid obesity? However, strategies for partially blocking MDSC functions should be counted to ensure the maintenance of their ability to restore insulin sensitivity while simultaneously preventing their capacity to restrain the antitumor immune response,” the researchers wrote.