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Deregulation of Immune System in Gastric
https://t.me/med1917
Cancer Development, How Immune
Nutrition Might Restore the Functions
of Immune Cells
Luigi Spagnoli, Federica Petrelli, Bruno Perotti, Marco Arganini,
and Maria Raffaella Ambrosio
Abstract
Gastric carcinoma (GC) is one of the most frequent neoplasms around the world
and still remains the second cause of death of all malignancies worldwide, even if
a steady decline in the incidence rate has been observed in the last few decades.
Studies on the genetic landscape of GC have been published, and a molecular
classification has been proposed, focusing on the possibility of using a specific
target therapy for each group of patients. During the past few years, immunother-
apy has become one of the most widely applied therapies in the treatment of
advanced neoplasm, including GC. Unfortunately, positive responses to immu-
notherapy are limited to a small fraction of patients with GC, and, due to tumour
heterogeneity, its efficacy remains to be better understood. One of the reasons
could be the ability of the tumour to escape the immune system. Therefore, more
recently, many efforts have been spent to find strategies aimed at enhancing the
host defence mechanisms. Among these, immune nutrition (IN) seemed to be
promising.
IN has the ability to reduce hospital stay and the health system costs and
to improve the nutritional status, metabolism, incidence of post-operative
complications, adherence to anticancer therapies, quality of life (QOL), and,
ultimately, survival. In fact, by IN, the balance between the immunological
system and the tumour is shifted towards giving more strength to the immunological response. Although further studies are needed to optimize IN protocols
and confirm their prognostic impact, our review seems to support the rationale for
L. Spagnoli · F. Petrelli · M. R. Ambrosio (✉)
Pathology Unit, U.O.C. Anatomia Patologica, Azienda Toscana Nord Ovest, Pisa, Italy
e-mail: mariaraffaella.ambrosio@uslnordovest.toscana.it; maradot@libero.it
B. Perotti · M. Arganini
Surgery Unit, Azienda Toscana Nord Ovest, Pisa, Italy
#
The Author(s), under exclusive license to Springer Nature Switzerland AG 2023
Interdisciplinary Cancer Research, https://doi.org/10.1007/16833_2023_184
Published online: 7 October 2023
101
102 L. Spagnoli et al.
https://t.me/med1917
implementing IN in the routine management of patients undergoing elective
surgery for GC.
Keywords
Gastric cancer · Immune nutrition · Immune system · Immunity · Immunotherapy
1 Introduction
1.1 Epidemiology and Pathogenesis
Gastric carcinoma (GC) is a multifactor disease: 90% of causes are sporadic and the
other 10% develop in a familial/hereditary setting (Jemal et al. 2011). According to
the last statistics from the International Agency for Research on Cancer (IARC), GC
is the fifth most common cancer worldwide and the fourth cause of cancer-related
death with 768,793 new deaths in 2020 (Ladeiras-Lopes et al. 2008). The incidence
shows wide geographical variation, ranging from 75,3% of cancers in Asia to 2,7%
in North America (Sitarz et al. 2018). The higher risk areas are China and Japan,
whereas the lower risk ones are North America and Oceania (Lin et al. 2014). GC
affects more frequently men (M:F = 2:1) in their fifth decade of life. Although GC is
often reported as a single entity, it can be generally classified into two subsites,
which differ in terms of anatomic topography, epidemiology and carcinogenesis.
Non-cardial GC develops in the lower stomach (antrum and pylorus) and represents
the majority (80%) of GC in higher incidence countries, and almost all cases are
attributable to chronic infections by Helicobacter pylori that leads to atrophic
gastritis and intestinal metaplasia in a stepwise progression known as Correa’s
cascade (Serizawa et al. 2015). Although only 5% of infected patients will develop
GC, H. pylori is classified as class I carcinogenic by the IARC because it induces
DNA mutations and epigenetic changes. The extent to which H. pylori favours
neoplastic transformation likely depends on bacterial genetic [vacuolating toxin
(vacA) versus cytotoxicity-associated immunodominant antigen (cagA) antibodies],
host genetics [single-nucleotide polymorphism of Interleukin1B (IL1B) and Tumor
Necrosis Factor (TNF) genes], age of infection acquisition and environmental
factors. Established risk factors beyond H. pylori for non-cardial gastric cancer
include tobacc o smoking, alcohol intake and high consumption of food preserved
in salt, processed meat and grilled or barbecued meat and fish (Munoz and
Franceschi 1997; Nishino et al. 2006). Less common risk factors include obesity
and autoimmune gastritis (Massarrat and Stolte 2014; Buckland et al. 2015).
Cardial GC develops in the upper stomach (cardia), mainly affects men in the
seventh decade of life and represents 50–60% of GC in North Europe and USA. Risk
factors include gastro-esophageal reflux disease and obesity.
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