ω3 Polyunsaturated Fatty Acids as Immunomodulators in Colorectal Cancer: New Potential Role in Adjuvant Therapies

Abstract

Diet composition may affect the onset and progression of chronic degenerative diseases, including cancer, whose pathogenesis relies on inflammatory processes. Growing evidence indicates that diet and its components critically contribute to human health, affecting the immune system, secretion of adipokines, and metabolic pathways. Colorectal cancer (CRC) is one of the leading causes of death worldwide. Antineoplastic drugs are widely used for CRC treatment, but drug resistance and/or off-target toxicity limit their efficacy. Dietary ω3 polyunsaturated fatty acids (PUFA) have been gaining great interest in recent years as possible anti-inflammatory and anticancer agents, especially in areas such as the large bowel, where the pro-inflammatory context promotes virtually all steps of colon carcinogenesis. Growing epidemiological, experimental, and clinical evidence suggests that ω3 PUFA may play a role in several stages of CRC management exhibiting antineoplastic activity against human CRC cells, improving the efficacy of radiation and chemotherapy, ameliorating cancer-associated secondary complications, and preventing CRC recurrence. These effects are most likely related to the immunomodulatory activities of ω3 PUFA that are able to influence several aspects of the inflammatory process ranging from inflammasome activation, leukocyte recruitment, production of immune mediators to differentiation, and activation of immune cells. In this review, we will focus on the potential use of ω3 PUFA as adjuvant agents together with chemo/radiotherapy, highlighting the immunomodulatory effects most likely responsible for their beneficial effects in different stages of CRC management.

Marine omega‐3 fatty acid intake and survival of stage III colon cancer according to tumor molecular markers in NCCTG Phase III trial N0147 (Alliance)

“…While newly approved immunotherapeutic agents for treating MSI tumors has shown great promise, the clinical efficacy remains suboptimal, with a response rate of 30–50% in the recent phase II trials . Therefore, given the well‐known immunomodulatory activity and the observed benefit of MO3PUFA for MSI tumors in our studies, it is possible that integrating MO3PUFA into the current immunotherapeutic regimen may help improve treatment outcome …”

Eicosapentaenoic acid and/or aspirin for preventing colorectal adenomas during colonoscopic surveillance in the NHS Bowel Cancer Screening Programme: the seAFOod RCT

“…159 However, regulation of host immune surveillance as a mechanism of primary CRC chemoprevention activity remains a valid hypothesis for both seAFOod trial interventions. 160 We have recently reported that mixed ω-3 PUFA treatment is associated with an increase in abundance of SCFA-producing bacteria in the colon. 129 The hypothesis that the propensity for EPA benefit in the distal colorectum relates to increased anticarcinogenic SCFA-FFAR2 signalling 132 should now be tested by measuring stool SCFA concentrations in human studies, in parallel with FFAR2 expression studies using rectal mucosa from the seAFOod trial biobank.…”

Decreased Triacylglycerol Content and Elevated Contents of Cell Membrane Lipids in Colorectal Cancer Tissue: A Lipidomic Study

“…Given the important role of lipids at various levels of cell physiology, changes in their metabolism may interfere with a variety of processes, e.g., the control of the plasticity and organization of plasma membranes, or the provision of substrates for ATP synthesis and cell signaling [3]. Some authors have claimed a positive effect of supplementation with various lipids [2,6] or their main structural elements, fatty acids (FAs), in cancer patients [7]. However, the effects of FAs were also shown to depend on the structural group they belong, as well as on their source (de novo synthesis, diet) [3].…”