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The GC arising in a familial/hereditary setting include:
(A) Hereditary diffuse GC (HDGC): it is an autosomal dominant cancer susceptibil-
ity syndrome characterized by diffuse-type GC and invasive lobular breast
cancer, mainly caused by inactivating germline mutation in CDH1 gene
encoding E-cadherin, a molecule involved in cell-to-cell adhesion. The prevalence of HDGC is <1% of all GC cases. Two histological forms have been
identified:
– Early HDGC: it is characterized by multiple foci of invasive signet-ring cell
carcinoma (<0.1–10 mm) in the super ficial gastric mucosa, without nodal
metastasis; in most patients, no intestinal metaplasia or Helicobacter pylori
infection is present. It may remain indolent for a long time and carry a very
low risk for dissemination.
– Advanced HDGC: it shows the characteristic picture of diffuse type, poorly
cohesive GC; usually, tumours are heterogeneous, displaying atypical cells
with diffuse growth and also cords, micro-gl ands and small mucin lakes and,
in most cases, there is at least a small percentage of typical signet-ring cells.
It has a poor prognosis.
(B) Lynch syndrome: it is an autosomal dominant hereditary disorder due to muta-
tion in a mismatch repair (MMR) gene, most commonly a germline mutation in
MSH2 or MLH1, less frequently due to germline mutations in MSH6 or PMS2.
Also, mutations in epithelial cellular adhesion molecule (EPCAM)/tumourassociated calcium signal transducer 1 (TACSTD1) gene, inactivation through
germline promoter hypermethylation of MutL homolog 1 (MLH1) and, rarely,
inactivation of cell cycle checkpoint kinase 2 (CHEK2) may result in Lynch
syndrome. Eighty percent of patients with this syndrome develop colorectal
carcinoma and also present increased risk of endometrial carcinoma, ovarian
carcinoma and cancers of small bowel, stomach, upper urinary tract and brain.
They tend to develop carcinomas at an earlier age than the general population.
(C) Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS): it is
an autosomal dominant cancer predisposition syndrome associated with an
increased risk of gastric adenocarcinoma, together with proximal polyposis of
the stomach, and it is considered part of familial adenomatous polyposis since it
involves the antigen-presenting cell (APC) gene, but it has a unique phenotype.
(D) Juvenile polyposis syndrome (JPS): it is an autosomal dominant syndrome
characterized by multiple juvenile polyps of the gastrointestinal tract, predominantly of the colon rectum (ranging from 1 to 100), and also of the stomach and
the small intestine, found respectively in 85% and 14–33% of patients. Its
incidence has been estimated to be 1 case per 100.000–160.000 person-year
in Europe. A germline mutation in SMAD4 or BMPR1A is identified in 50–60%
of patients.
(E) Peutz–Jeghers syndrome (PJS): it is an autosomal polyp and cancer predisposi-
tion syndrome characterized by mucocutaneous melanin pigmentation and
gastrointestinal polyposis; about 95% of patients with PJS present polyps in
the small intestine and, in 25% of cases, in colon and stomach. In 90% of
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patients, a germline mutation, mainly point mutation and small intragenic
deletions, in STK11 gene can be found. The prognosis for patients with PJS is
determined by the risk of malignancy and gastrointestinal complications, such as
small bowel intussusception.
(F) Cowden syndrome (CS): it is an autosomal dominant disorder characterized by
multiple hamartomas involving organs derived from any of the three germ
layers, with cancer predisposition, caused by germline mutation of the PTEN
gene in 85% of cases.
The prognosis for patients with GAPPS, JPS, PJS and CS is now mainly
determined by the risk of malignancy. Therefore, a close surveillance is
recommended (Sitarz et al. 2018).
1.2 Histology
The most commonly used pathological classifications for GC cancer are:
(A) WHO: it includes papillary, tubular, poorly cohesive (either with signet-ring cell
phenotype or with other cell types), mucinous and mixed histological patterns
(Marano et al. 2022;Rovielloetal.2022). Other rare subtypes are gastric
adenocarcinoma with lymphoid stroma, hepatoid adenocarcinoma, micropapillary
adenocarcinoma and gastric adenocarcinoma of fundic gland type (Nagtegaal et al.
2020;Ohetal.2018).
(B) Lauren: it comprises intestinal, diffuse, mixed and indeterminate type
(Nagtegaal et al. 2020).
(C) Japanese Gastric Cancer Association (JGCA): it includes papillary, tubular
1 and tubular 2, poorly 1 (solid type), signet-ring cell, poorly 2 (non-solid
type) and mucinous histotypes (Nagtegaal et al. 2020).
1.3 Molecular Landscape
During the last few years, many studies on the genetic landscape of GC have been
published and, as a result, a molecular classification has been proposed. It includes
four subtypes of GC, suggesting a possible relation between genotype and phenotype (Röcken 2017; Marrelli et al. 2022). The four genetic subtypes are:
(A) Microsatellite instable GC (MSI-GC): it represents 0–44.5% of all GC (Mathiak
et al. 2017) cases and is more prevalent in elderly patients suffering from distal
GC. The evaluation of the microsatellite state can be performed by immunohistochemistry for MLH1, PMS2, MLH2 and MSH6 proteins and by mononucleotide markers BAT-25, BAT-26, NR-21, NR-24 and NR-27 (Mathiak et al.
2017). In GC, microsatellite instability (MSI) is usually secondary to silencing
of MLH1 gene and lack of expression of the encoded protein. The evaluation of
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MSI has a significant impact on clinical decis ion-making for two reasons:
MSI-GCs may not require any standard adjuvant chemo- and/or radiotherapy
in a curative setting (Mathiak et al. 2017); MSI-GCs generally express the
immune checkpoi nt molecules PD-L1 and PD-1 and may be considered for
the treatment with immune checkpoint inhibitors (ICIs) in the palliative setting
(Böger et al. 2016; Suh et al. 2020).
(B) Epstein–Barr virus–associated GC (EBV-GC): it represents 10% of all GCs in
Asian population, but only 0–5% in Western population. It has a male predominance and occurs mainly in proximal and post-gastrectomy GC (Fukayama and
Ushiku 2011; Liu et al. 2015; Piccaluga et al. 2018). The phenotype of EBV-GC
is variable with tubular and intestinal differentiation as well as an undifferentiated phenotype (lymphoepithelioma-like or medullary). EBV presence is shown
by checking the Epstein–Barr virus–encoded small RNAs (EBER) through in
situ hybridization (ISH).
Any GC with an unusual phenotype should be tested for EBV infection by
EBER-ISH. Similar to MSI-GC, EBV-GCs significantly more commonly
express PD-L1 and PD-1 and might thus be sensitive to therapy with immune
checkpoint inhibitors (Böger et al. 2016). EBVGC and MSI-GC are mutually
exclusive (Mathiak et al. 2017).
(C) Chromosomally instable GCs: it represents 37–40% of all GCs; it has a male
prevalence and affects more commonly the distal stomach. The chromosomally
instable GCs often show an intestinal phenotype according to Lauren, frequently harbour mutations in the P53-tumour suppressor gene and activate
mutations in genes coding for tyrosine kinase receptors such as epidermal
growth factor receptor (EGFR), fibroblast growth factor receptor 2
(FGFR2), human epidermal growth factor receptor 2 (HER2) (Warneke et al.
2013; Shen et al. 2016), and mesenchymal epithelial transition factor (MET)
(Deng et al. 2012; Kiyose et al. 2012; Sade-Feldman et al. 2013; Metzger et al.
2016).
(D) Genomically stable GCs: it represents 10–15% of all GCs and affects more
frequently males suffering from distal GCs. Genomically stable GCs show a
diffuse histological phenotype according to Lauren and harbour CDH1 and
RHOA mutations as well as rearrangements between CLDN18 and ARHGAP26
or ARHGAP6 (Suh et al. 2020; Kakiuchi et al. 2014).
We are carrying out with the Italian Group for GC Research (GIRCG) a
multicentric study involving other institutions to evaluate the reproducibility of
molecular classification by immunohistochemical and ISH analysis. Speci
cally, we are investigating the expression of MLH-1, PMS-2, MSH -2, MSH-6,
E-cadherin, p53, HER-2, EBER-ISH and PD-L1 proteins on biopsies and
surgical specimens, to evaluate if the bioptic specimens are representative of
the whole tumour in view of the heterogeneity of GCs.
fi-
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1.4 Tumour Microenvironment
During the past few years, immunotherapy has become one of the most widely used
therapies in the treatment of advanced neoplasm, including GC (Lordick et al. 2017).
Unfortunately, positive responses to immunotherapy are limited to a small fraction
of patients with GC, and, due to tumour heterogeneity, its efficacy rema ins to be
better understood (Zeng et al. 2019; Salati et al. 2019; Lee et al. 2014). A clear
understanding of immunotherapy mechanisms is a priority for the management and
extension of positive responses to broader target populations.
The tumour microenvironment (TME) is a complex system composed of a wide
spectrum of cell types that contribute to cancer initiation, grow th, and dissemination
(Hanahan and Weinberg 2011). The primary components of TME include immune
cells, fibroblasts, endothelial cells, along with their secreted extracellular matrix
(ECM) (Kobayashi et al. 2019), cytokines and chemokines recruited by neoplastic
cells (Bockerstett and DiPaolo 2017).
The most important components of TME are:
(A) Cancer-associated fibroblasts (CAFs): they are a dominant stromal component
of the TME and can produce abundant soluble molecules, including basic
fibroblast growth factor (bFGF), members of the vascular endothelial growth
factor (VEGF) family, platelet-derived growth factor (PDGF), ligands of epidermal growth factor receptor (EGFR), interleukins and tumour growth factor-β
(TGF-β). These molecules collaborate to regulate tumour growth and inflammatory responses via direct cell-to-cell contact or in a paracrine way (Sh ibata
et al. 2013 ; Huang et al. 2014 ; Mizutani et al. 2019).
(B) Immune cells: a large number of immune cells are involved in the tumour
microenvironment, including:
(a) Macrophages: tumour-associated macrophages (TAMs) are among the most
abundant immune cells. The degree of TAM infiltration in tumour tissue is
positively related with poor prognosis. TAMs, in fact, can promote cancer
progression by secreting various factors, including inflammatory cytokines,
growth factors and proteolytic enzymes. In addition, TAMs can interact with
other stromal components and often can suppress the host immune response,
resulting in tumour immune escape and the subsequent uncontrolled growth
of tumour cells (Pan et al. 2020). Macrophages are divided into two main
groups: M1 and M2. M1 macrophages have a pro-inflammatory role and are
responsible for the production of various cytokines. Conversely, M2 polarization of macrophages are driven by TH2 cells, basophils and type 2 innate
lymphoid cells (ILC2s) through the production of IL-4, IL31 and/or IL-33
(Biswas and Mantovani 2010; Petersen et al. 2018). There is a direct
connection between tumour cells and TAMs. In fact, tumour cells can
secrete several cytokines and growth facto rs that induce M2 polarization
in TAMs. TAMs, on the other hand, can directly stimulate tumour cell
growth by secreting EGF, hepatocyte growth factor (HGF), PDGF, fibroblast growth factor (FGF) and VEGF (Park et al. 2015; Zhao et al. 2016;
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Song et al. 2019). M2 macrophages can be reprogrammed into M1 phenotype by interfering with these interactive signals, leading to a shift in
immune microenvironment (Veremeyko et al. 2018; Zhang et al. 2019).
(b) Myeloid-derived suppressor cells (MDSCs): they comprise a population of
myeloid progenitor and immature myeloid cells and are regulatory immune
cells associated with the site of chronic inflammation and cancer that
suppress CD8-positive T cell function by their expression of PD-L1 and
CTLA-4 (Katoh et al. 2013). MDSCs also have the ability to suppress host
immunity through the production of Arg-1, Nitric Oxide Synthase (iNOS)
and Reactive Oxygen Species (ROS), such as macrophages (Gabrilovich
and Nagaraj 2009; Asfaha et al. 2013).
(c) Lymphocytes: tumour-infiltrating lymphocytes (TILs) consist of T cells,
B cells and natural killer (NK) cells; T cell–mediated adaptive immunity is
considered to play an important role in anti-tumour immunity. The subset of
T cells involved in this process are:
– CD8-positive cytotoxic T cells are generally responsible for the destruc-
tion of virus-infected cells and tumour cells and are also implicated in
transplant rejection.
– CD4-positive T helper (TH) cells have a role in assisting other lympho-
cyte functions, including the maturation of B cells into plasma cells and
memory B cells and the activation of cytotoxic T cells and macrophages.
– FOXP3-positive regulatory T cells are crucial for the maintenance of
immunological tolerance. Their major role is to shut down T cell–
mediated immunity towards the end of an immune reaction and to
suppress autoreactive T cells that escaped the process of negative selection in the thymus. Two major classes of CD4-positive T-reg cells have
been described, namely FOXP3-positive T-reg cells and FOXP3negative T-reg cells (Abbas et al. 2013 ).
– PD1-positive-exhausted CD8-positive T cells are characteri zed by a low
expression of T-bet and TCF1, high expres sion of Eomes and TOX and a
lower proliferative status, generally in the context of suppressive tumour
microenvironment and prolonged antigen exposure (Al-Shura 2020).
A higher number of both T-reg and T-exhausted cells is associated
with poor prognosis.
– Memory T cells improve the immune response after the reintroduction of
a relevant pathogen into the body (Sallusto et al. 1999).
– NK cells are a type of cytotoxic lymphocyte critical to the innate immune
system that belong to the large family of innate lymphoid cells (ILCs).
The role of NK cells is analogous to that of cytotoxic T cells.
(d) Endothelial cells: endothelial and vascular blood vessel cells have a func-
tion beyond supplying nutrition to tumour tissues; they also act as cancer
niche cells and create a cancer-promoting environment (Butl er et al.
2010). It has been suggested that the perivascular network is important in
the metastasis of various types of cancers, including GC (Wang et al.
2017; Kim et al. 2019). A potential way in which vascular endothelial
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cells could promote metastasis is by the activation of tumour cells by locally
invaded vessels or endothelial cells, which induce epithelial-to-mesenchymal transition (EMT) and allow the neoplastic cells to enter systemic
circulation more rapidly (Marrelli et al. 2022). In addition, circulating
tumour cells and/or tumour-derived soluble factors may influence vascular
formation and other features in distant organs, creat ing a more favourable
microenvironment for neoplastic cells (Gil et al. 2013; Wu et al. 2017;
Yang et al. 2020; Liu and Cao 2016).
1.5 Tumour Immune Escape
Tumour immune escape has proved to be a tough barrier in cancer therapy. In fact, it
constitutes the set of all the strategies implemented by the neoplastic cells in order to
hide from the immune system, thus escaping its defence mechanisms, gaining the
ability to grow and proliferate in an immunocompetent environment (Patel et al.
2014). To achieve this ability, the neoplastic cells can activate the loss of antigenicity
and/or loss of immunogenicity. Loss of antigenicity consists in the acquisition of
defects in antigen processing and presentation. Alternatively, the loss of immunogenic tumour antigens leads to the lack of immunogenic peptides presented in the
context of a peptide/major histocompatibility complex (MHC) complex (Oshima
et al. 2013). Downregulation or loss of MHC I and/or MHC I–related protein
expression on tumour cells prevents the inhibition of NK cells, thus enabling
subsequent lysis of the tumour cell through the release of cytolytic granules and
induction of apoptosis (Mohme et al. 2017). The impairment of antigen presentation
impacts the TME as a result of a combination of fewer invading APCs and their
malfunction, which means that tumour cells can evade immune monitoring and
clearance due to the combined effects of inefficient tumour-associated antigens
and defective antigen presentation mechanisms (Silva et al. 2018; Wang et al.
2022). Those tumour cells that can avoid being eliminated by the immune system
join with other local cells and cytokines, interfering in many signalling pathways, to
create an immunosuppressive microenvironment that aids in growth and survival. In
fact, cancer cells can modulate the functions of various cellular components of TME
(stromal cells, fibroblasts, fat cells, vascular endothelial cells, TILs and TAMs)
orchestrating an immunosuppressive environment. TILs, which have the propensity
to mount an adaptive anti-tumour response, are present in many malignant tumours;
however, the immunosuppressive tumour microenvironment inhi bits the local activation and/or effector functions of these cells, leading to T cell exhaustion and
senescence (Beatty and Gladney 2015; Mohme et al. 2017). Additional immunosuppressive capacity consists of the expression of PD-L1 and the secretion of suppressive cytokines (e.g. IL-10, TGF-β). Furthermore, the production of tumour necrosis
factor alpha (TNF-α) and interleukin-6 (IL-6) by TAMs play a role positively
regulating PD-L1 (Wang et al. 2022).
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1.6 Immunotherapy in Gastric Cancer
Immunotherapy is considered an effective therapeutic strategy in medical oncology (Mellman 2011; Bang et al. 2010). Immune checkpoint inhibitors (ICIs), which
target pathways involved in immune regulation, help in breaking the cycle of
immune tolerance and allow T cell recognition against tumour cells. By inhibiting
the immune evasion induced by cancer cells, there is an increased immune response
against cancer (Pardoll 2012; Jacob 2015; Copp et al. 2016; Lonez et al. 2017).
GC is a malignancy with a high somatic mutational burden, which is a potential
marker for predicting response to ICIs. Moreover, the positive expression of PD-1
has been observed in 25–65% of patients with GC (Dolan and Gupta 2014). To date,
ICIs have been approved in advanced and metastatic GCs. However, accumulating
evidence suggests that patients with GC respond to immunotherapy in various
settings (Galdy et al. 2016 ).
Therefore, in the near future, immunotherapy will also be used in early resectable
GCs and as neo-adjuvant therapy in combination with standard chemotherapy
(Sundar et al. 2018).
Biomarkers for GC immunotherapy include:
(A) MSI-MMR: GC with deficient DNA mismatch repair detected by immunohis-
tochemistry show a good response to ICIs in a tissue-diagnostic manner.
According to Keynotes -181 and -158, MMR deficient GC may benefit from
prembrolizumab in monotherapy as second-line treatment in non-resectable and
metastatic GCs (Pan et al. 2018; Casak et al. 2021).
(B) EBV: EBER-ISH positivity is a potential predictive biomarker for immunother-
apy response by nivolumab and prembrolizumab.
(C) PD-L1: it is the most well-known biomarker for predicting response to immu-
notherapy. A value of PD-L1 expression (as detected by the combined positive
score – CPS > 5) is the cut off for the first-line treatment with nivolumab in
combination with platinum and fluoropyrimidine for advanced/metastatic
unresectable HER2 negative GC (Gerson et al. 2017).
More recently, prembrolizumab has been approved in combination with platinum
and fluoropyrimidine as first-line treatment for non-resectable or advanced GC with
CPS ≥ 10.
2 Immune Nutrition
The potential to modulate the activity of the immune system by the subministration
of specific nutrients is called IN. This concept can be applied to any situation in
which a particular combination of nutrients is used to modify inflammatory or
immune responses. However, in the last few years, IN has become part of the
enhanced recovery after surgery (ERAS) protocol for the management of patients
admitted to major abdominal surgery. This was done with the aim to reduce surgical
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stress, enhanced recovery, improve clinical outcome. Patients affected by gastrointestinal cancers are usually malnourished due to the insufficient nutritional intake
and the long-term tumour consumption before surgery. Therefore, they often require
an exogenous supply of nutrients through the parenteral or enteral routes. In addition, the high cellular turnover during tumourigenesis leads to a dysregulation of the
host immune response. This, together with the surgery-related systemic inflammatory response syndrome, impairs the immune response. Immunosuppression also
increases the risk of morb idity and mortality due to infection and to post-operative
complications. Enhance host defense mechanisms and modulate the inflammatory
response to stress in the pre-operative and post-operative period may help patients
recover and outcome (Caglayan et al. 2012).
2.1 Immune Nutrition in Gastric Cancer
In patients with GC, malnutrition is caused by a decrease in food intake due to
mechanical obstruction and cachexia, which occur during cancer progression.
Cachexia is associated with dysregulation of tumour necrosis factor-α, interleukin1, interleukin-6 and leptin. These factors may significantly influence appetite,
muscle mass and adipose tissues, leading to weight loss (Senkal et al. 1995).
Therefore, many patients with advanced GC often develop hypoproteinemia, dehydration and electrolyte abnormalities.
Pre-operative malnutrition may therefore contribute to post-operative
complications and poor prognosis. Moreover, post-operative complications can
adversely affect the overall and recurrence-free survival of patients with GC
(Weimann et al. 2017). Therefore, an appropriate assessment of the pre-operative
nutritional status through various biochemical and physiological tests and subsequent
nutritional intervention before surgery is essential for patients with GC. The
nutritional evaluation status of the patient is usually performed by evaluating body
weight, body mass index and nutritional risk score and by applying the criteria for
diagnosis of mal nutrition of Global Leadership Initiative on Malnutrition (GLIM)
(Jensen et al. 2019).
Many types of nutrients are used, each of which contains distinctive supplements.
The nutrients most often studied for IN are arginine, glutamine, branched chain
amino acids, n-3 fatty acids and nucleotides (Song et al. 2015; Braga et al. 2002;
Chang and Bistrian 1998; Napolitano et al. 1999; Lara and Jacobs 1998).
Combinations of some or all of these nutrients are most often used. Therefore,
they should be administered according to the nutritional status of each patient by
oral and enteral ways.
However, some surgeons did not find it to be of much help, mainly because GC
patients are often in advanced stage s, requiring emergency/urgent surgery and
enteral nutrition due to obstruction. Nonetheless, both American Society for Parenteral and Enteral Nutrition (ASPEN) and European Society for Parenteral and
Enteral Nutrition (ESPEN) guidelines (Weimann et al. 2017) suggest starting enteral
immune nutrition (EN) 7 days before surgery.
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An important meta-analysis suggested that IN effectively increases the level of
IgA, IgG, IgM, CD4þ, CD3þ, CD4þ/CD8þ ratio and the count of NK cells, improving the nutritional and immunological status of GC patients undergoing gastrectomy.
A recent meta-analysis found that EN boosts the immunity of GC patients
undergoing surgery. Moreover, by pooling the results of several randomized control
trials, it emerges that IN reduces the length of stay, post-operatory complications and
hospital costs.
2.2 Effects of Immune Nutrition on Tumour Microenvironment
To date, there are some concerns about the potential impact of IN on tumour biology,
and no clinical evidence have been produce d regarding its effects on TME.
Our group carried out a recent study about IN and its impact on TME (D’ Ignazio
et al. 2020). We focused on analysing how IN can influence the cell-mediated
immune response in the microenvironment of gastric and colorectal cancers: we
evaluated the composition of TME cells before (on the biopsy) and after (on the
surgical sample) the administration of IN. As proof of principle, immunomicroenvironment of non-neoplastic tissues (i.e. sleeve gastrectomies and colons
for diverticulitis) was also studied, and the results were compared.
The TME was studied in a total of 24 samples by immunohistochemistry;
specifically, 16 samples from patients receiving IN before surgery and 8 from
patients following the standard nutrition. The samples were paired with the respective pre-operative biopsies. Moreover, we examined the TME in non-neoplastic
(n = 10) surgical specimens. Interestingly, by comparing infiltrating immune cell
populations before (on the biopsy) and after (on the matched surgical specimen) IN,
important changes in TME were found in patients managed with immunonutrient
supplementation. More specifically, the analysis of the surgical specimens after IN
showed a higher number of Cytotoxic T Lymphocytes (CTL), TH lymphocytes,
APC and a decrease of cells showing a T-exh and a T-reg phenotype and M1
polarization. Also, NK cells were decreased. Moreover, both cancer cells and
TME inflammatory cells showed a lower expression of PD-L1. These differences
were proved to be statistically significant for all cells evaluated ( p < 0.05). On the
other hand, in patients treated with standard nutrition in the pre-operative period, no
significant changes in in filtrating lymphocytes ( p = 0.5) and PD-L1 expression
( p = 0.3) were found, comparing the biopsy and surgical specimen. Finally, the
comparison of surgical samples between patients in the IN and the non-IN groups
demonstrated a higher number of CTL and TH lymphocytes, NK cells, APCs and
from M2 to M1-TAM along with low levels of PD-L1 expression in TME,
suggesting an enhanced immune response in the former group.
In non-neoplastic patients, no expression of molecules involved in tumour
immune response was found. The CD4 and CD8 T cells were within the normal
number; the few macrophages detected showed a M1 phenotype, and no activation
of APC cells was identified.
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These data support the view that IN might restore the functions of immune cells
also by reverting M2 polarization and PD-1/PD-L1 pathway induction.
Based on the result of this pivotal study, a larger research is ongoing in our
institution thanks to the collaboration of GIRCG. Our goal is to assess if IN improves
the surgical and oncological long-term outcome of GC patients, and if it may be used
as an enhancer of the already available therapeutic protocol. Moreover, by a deep
characterization of GC TME, we would establish a potential subgroup of tumours
with a higher tendency for evolution and progression.
3 Conclusion
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. Since the last decade, great attention has been given
to the immunological set-up of patients undergoing abdominal surgery for cancer
and the amount of data is still growing. Immunosuppression is accentuated, and the
challenge between the host ’ s defence and possible contaminating microorganism is
critical, leading to a higher percentage of infectious events and influencing the postoperative outcome (Aida et al. 2014). 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. In this scenario, IN could represent and enhance of the
therapy to be included in the usual guidelines as chemotherapy or surgery (D’Ignazio
et al. 2020 ).
To date, research has been mainly focused on the clinical course after surgery and
surgical complications. The effects of IN on single cancer cells, TME and on
immunological pathways acting against cancer have not been explored enough.
Accordingly, our ongoing study aims to address these issues and to explain the
ways by which immune nutrition can impact TME.
By IN, the balance between immunological system and tumour seems to be
shifted towards giving more strength to immunological response. Therefore, the
goal should be to add microenvironmental data to hist ological characteristics and
molecular pattern, aiming to better characterize the behaviour of each single tumour,
leading to a more tailored approach.
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Al-Shura AN (2020). Lymphocytes. In: Advanced hematology in integrated cardiovascular Chinese
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