Dear Colleagues,

Cancer is known to break the metabolic balance and immunological competence, leading to a decreased response to surgical injury and favouring tumour relapse, progression and tissue invasion. Oncological patients have a higher risk of malnutrition because of reduced food intake as well as disease-related pathologies such as increased muscular catabolism and chronic inflammation, which may aggravate their nutritional status. One of the mechanisms by which a neoplasm could grow and metastasize is the tumour immune escape by avoiding recognition and attack from the immune system. The tumour immune escape acts through two main mechanisms. The first is by modulating the tumour microenvironment represented by stromal cells, fibroblasts, fat cells, vascular endothelial cells, immune cells (the so-called TILs) and tumour-associated macrophages. Tumour-induced immunosuppression prompts immunosuppressive cells to accumulate around the tumour and secreted immunosuppressive factors, which inactivate cytolytic CD-8 positive T lymphocytes in order to decrease the immune tolerance of tumour cells, such as regulatory T cells (T reg cells), dendritic cells (DCs), and M2 macrophages. The second mechanism of immunosuppression involves induction of the immunosuppressive molecules or their receptors, including programmed death-ligand 1/programmed death-1 (PDL1/PD-1) which can inhibit the activation of effector T lymphocytes, ultimately leading to tumour immune escape.

Published evidence suggests that enteral immunonutrition (EIN) enriched with at least two of the following substrates—arginine (Arg), omega-3-fatty acids (v-3-FA), glutamine (Glu), or ribonucleic acid (RNA)—has the potential to decrease the infection risk and shorten the length of postoperative hospitalization. Various timings of EIN administration, including preoperative, postoperative, and perioperative periods, have been studied.

Although many studies present non-conclusive or conflicting results, comparing different timings of nutritional intervention, it is generally agreed that preoperative nutrition is most beneficial for surgical patients. ESPEN guidelines suggest the beginning of EIN from seven days before surgery for malnourished patients even if the operation has to be delayed. Similar results have been shown for normo-nourished cancer patients.

An important meta-analysis suggests that EIN effectively increased the level of IgA, IgG, IgM, CD4þ, CD3þ, CD4þ/CD8þ ratio, and the count of NK cells, improving the nutritional and immunological status of gastric cancer (GC) patients undergoing gastrectomy. Aida et al. demonstrated that immunonutrition with arginine and omega-3 fatty acid supplementation might modulate Th1/Th2 differentiation and IFN-g production inciting host defence against pathogens.

All studies up to date in the gastrointestinal cancer field focused on the postoperative outcomes of immunonutrition, and so far, few data are available on its impact on tumour immuno-microenvironment.

A better understanding of the impact of immune nutrition on cancer destiny may open new therapeutic options. In fact, in the near future, we could potentially identify the subgroup of tumours that are more responsive to immunotherapy and use immunonutrition as an enhancer of the therapies already included in the usual guidelines as chemotherapy or surgery.

Dr. Maria Raffaella Ambrosio
Dr. Luigi Marano
Guest Editors

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• immune nutrition
• tumor microenvironment
• immune escape
• cancer
• malnutrition
• diet and supplementation
• nutrients
• enteral nutrition
• inflammation
• muscle 
• preoperative, postoperative, and perioperative