Prevention and treatment of cancers by immune modulating nutrients

Abstract

Epidemiological and laboratory data support the protective effects of bioactive nutrients in our diets for various diseases. Along with various factors, such as genetic history, alcohol, smoking, exercise, and dietary choices play a vital role in affecting an individual's immune responses toward a transforming cell, by either preventing or accelerating a neoplastic transformation. Ample evidence suggests that dietary nutrients control the inflammatory and protumorigenic responses in immune cells. Immunoprevention is usually associated with the modulation of immune responses that help in resolving the inflammation, thus improving clinical outcome. Various metabolic pathway-related nutrients, including glutamine, arginine, vitamins, minerals, and long-chain fatty acids, are important components of immunonutrient mixes. Epidemiological studies related to these substances have reported different results, with no or minimal effects. However, several studies suggest that these nutrients may have immune-modulating effects that may lower cancer risk. Preclinical studies submit that most of these components may provide beneficial effects. The present review discusses the available data, the immune-modulating functions of these nutrients, and how these substances could be used to study immune modulation in a neoplastic environment. Further research will help to determine whether the mechanistic signaling pathways in immune cells altered by nutrients can be exploited for cancer prevention and treatment.

Keywords: Bioactive agents; Cancer; Immune modulation; Macronutrients; Phytochemicals.

Fig 1A:

Arginine and glutamine levels are to be balanced to achieve its tumor inhibiting functions. Both low levels and high levels of arginine is having negative effects on immune responses and tumor tissues. Low levels of arginine will lead to reduced infiltration of lymphocytes in tumor microenvironment. However, increased levels of arginine will eventually lead to sustained continuous production of NO and high levels of polyamines which help in tumor cell proliferation and development. Hence, a balanced concentrations of arginine is necessary for achieving best tumor inhibiting functions of arginine. B. A similar functions of glutamine are being discussed in this review. Lower glutamine levels results in reducing cytotoxic functions of NK cells leading to immune evasion of tumor cells. Increased levels of glutamine were reported in patients, resulting in increased T cells, and activation of DC in promoting TH17 immune cell responses, also resulting in tumor cell proliferation and tumor growth. Balancing the concentrations of glutamine is very important to achieve its beneficial effects on tumor inhibition.

Fig 2.

Tumor inhibitory functions of selenium: Selenium posses anti-inflammatory properties, along with other potent tumor inhibiting functions such as, inactivation of tumor cell promoting factors, blocking cell cycle regulation their by inhibit tumor invasion and metastases. Selenium is able to inhibit tumor-promoting functions by modulating various immune cell responses as listed above.

Fig 3A:

Anti-inflammatory and immune modulating effects of Phtochemicals. Curcumin enhances cytotoxicity of NK cells, and increase T effector, T memory cells and reduce T regulatory cells helping in inhibiting tumor growth. B. Flavanoids posses anti-inflammatory functions and also inhibit human pancreatic cancer stem cells. C. Stilbenes along with anti-inflammatory, anti-oxidant functions, it can polarize M1 and M2 macrophages helping in inhibition of tumors. D. Isothiocyanates increase proliferation of WBC cells. It can interact with Macrophage Inhibitory Factor (MIF) enhancing immune responses towards inhibition of tumor formation. Further, it was demonstrated to posses’ angiogenesis inhibitor properties.

Fig 4.

Polyunsaturated omega 3 fatty acids in inhibiting tumors. EPA and DHA interactions with lipid rafts in altering the immune cell responses and generate less potent 3 series and 5 series eicosanoid metabolites which will not promote tumor development