Mazzola et al. Immunity & Ageing 2012, 9:4
http://www.immunityageing.com/content/9/1/4
IMMUNITY & AGEING
REVIEW
Open Access
Aging, cancer, and cancer vaccines
Paolo Mazzola1,2†, Saba Radhi2†, Leonardo Mirandola2,3,4†, Giorgio Annoni1, Marjorie Jenkins3,4, Everardo Cobos2,4
and Maurizio Chiriva-Internati2,4*
Abstract
World population has experienced continuous growth since 1400 A.D. Current projections show a continued
increase - but a steady decline in the population growth rate - with the number expected to reach between 8 and
10.5 billion people within 40 years. The elderly population is rapidly rising: in 1950 there were 205 million people
aged 60 or older, while in 2000 there were 606 million. By 2050, the global population aged 60 or over is
projected to expand by more than three times, reaching nearly 2 billion people [1]. Most cancers are age-related
diseases: in the US, 50% of all malignancies occur in people aged 65-95. 60% of all cancers are expected to be
diagnosed in elderly patients by 2020 [2]. Further, cancer-related mortality increases with age: 70% of all
malignancy-related deaths are registered in people aged 65 years or older [3]. Here we introduce the microscopic
aspects of aging, the pro-inflammatory phenotype of the elderly, and the changes related to immunosenescence.
Then we deal with cancer disease and its development, the difficulty of treatment administration in the geriatric
population, and the importance of a comprehensive geriatric assessment. Finally, we aim to analyze the complex
interactions of aging with cancer and cancer vaccinology, and the importance of this last approach as a
complementary therapy to different levels of prevention and treatment. Cancer vaccines, in fact, should at present
be recommended in association to a stronger cancer prevention and conventional therapies (surgery,
chemotherapy, radiation therapy), both for curative and palliative intent, in order to reduce morbidity and mortality
associated to cancer progression.
Introduction
Elderly patients represent a unique and challenging
group of patients to the practicing oncologist. They
represent a heterogeneous group in terms of comorbidities and functional status which makes it difficult to
establish management recommendation. One of the cancer pathways that is of interest in the elderly is the
immune system and its role in oncogenesis and as
potential therapeutic targets. In this review we present
an overview of the changes in the immune system and
the use of cancer vaccines in the elderly. We will also
discuss the assessment of elderly patient with cancer.
Aging and immunosenescence
Aging is a process characterized by progressive functional decrease in all organs, morphological changes,
and immune system-related changes at the cellular and
* Correspondence: maurizio.chiriva@ttuhsc.edu
† Contributed equally
2
Department of Internal Medicine, Division of Hematology/Oncology, Texas
Tech University Health Sciences Center, 3601 4th St, Lubbock, TX 79430, USA
Full list of author information is available at the end of the article
molecular levels, which determine less adaptive biologic
functions. The immune system alterations in the elderly
are comprehensively known as immunosenescence [1].
This phenomenon is characterized by an accumulation
of changes that progressively results in dysfunctional or
compromised immune responses [2,3]. Multiple aspects
are involved: thymic involution [1], shifts in the number,
distribution, and activity of T- [4] and B-lymphocytes
[5-10], reduced availability of naïve CD4+ and CD8+ Tcells [1] and impaired production of naïve B-cells in
bone marrow [11-13], dysfunction of antigen presenting
cells (APCs) [3], alterations in cytokines production
[9-13], frequent oligoclonal and monoclonal immunoglobulin production [10-23], skewing of B cell production to CD5 + B cells that are more likely to generate
auto-antibodies [11-15].
In detail, overall diversity of the total T-cell repertoire
is skewed by oligoclonal expansions of memory CD4+,
CD8+[10-23] and CD95+ T-cells, and a limited production of naïve cells. Additionally, the increased memory
and activated effector CD8 + T-cells [24,25] show a
restricted TCR repertoire diversity, have shorter
© 2012 Mazzola et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
Mazzola et al. Immunity & Ageing 2012, 9:4
http://www.immunityageing.com/content/9/1/4
telomeres [26] and a limited proliferative potential [27].
They are largely represented by clonally expanded populations reactive towards cytomegalovirus (CMV) and
Epstein-Barr virus (EBV) determinants [24]. Such expansion significantly reduces T-cells available for responses
against other infections or cancer. Although the thymus
remains in part functionally competent [2], the diminished export rate associated with aging is insufficient to
replace peripheral naïve T-cells lost.
There is also evidence of an increased concentration
of IL-6, TNF-a, and various acute-phase proteins, suggesting that aging is associated with low-grade inflammatory phenotype [10-13,28,29], despite the absence of
any particular disease [30,31].
Consequently, due to these alterations in the adaptive
immune function, the elderly shows increased sensitivity
to infectious diseases and cancer, and poor responses to
vaccination [32,33]. Different studies have proven also
that cancer vaccines are less effective in older individuals than in young adults [3,10-23,34,35].
The chronic antigenic stress theory
Naïve T-cells able to specifically recognize a particular
antigen are usually very few. In order to efficiently
respond to an antigenic stimulus, they are able to
rapidly perform many cell divisions, producing multiple
clones. Once the acute antigenic challenge is resolved,
excess clones undergo apoptosis, and the organism
retains a certain number of memory cells [34]. If the
exposure of T-cells is prolonged, the antigenic stimulation could become chronic, potentially contributing to a
pro-inflammatory phenotype [35] and determining persistent T-cell clonal expansion. This scenario is commonly observed in the case of cancer (tumor-associated
antigens), autoimmunity, and during the aging process
(prevalently due to chronic stimulation by CMV antigens) [28,36]. The accumulated clones, whose number
(absolute number and number of expanded cell lines)
represents an important component to determine the
immune risk profile of an individual [28,29], physically
occupy a part of the “immunological space” [3] and
probably alternate/suppress the immune responses of
other specific clones [2]. Moreover, CMV-reactive
clones are dysfunctional: they present the characteristics
of anergic cells and a marked apoptosis resistance
[32,33]. A study from Mazzatti DJ et al. has also demonstrated that chronic antigenic stress leads to gene
expression changes in cultured T-cell clones [37].
Researchers have initially paid particular attention to the
CD8+ anti-viral effectors, but also the CD4+ T-helper
arm of the immune response seems to suffer the consequences of chronic CMV stimulation [38]. Whether this
chronic exposition to a number of antigens (CMV, EBV
[39], HIV [40], HCV [41], tumor antigens such as in
Page 2 of 11
melanoma [42,43]) has a role in driving immunosenescence needs to be further investigated, but the presence
of expanded dysfunctional T-cell clones and the comprehension of this phenomenon probably represents a
key factor for the development of new strategies of
immune intervention in the elderly.
Cancer immunoediting
Cancer Immunoediting
is a term coined by Schreiber and colleagues to describe
a process originating from the interaction between the
host immune system and tumor cells [6-23].
Although aimed to prevent auto-immunity, tolerance
can be directed towards non-self antigens, following a
process called induced tolerance. Cancer originates from
the transformation of the host cells: during this process,
multiple accumulating mutations turn the “self” into a
“non-self”. This transformation is expected to trigger an
immune response, but tumor immunity is different
because of a number of possible mechanisms of immune
evasion. The cancer cells often display weak immunogenicity, especially due to the lack or low expression of
co-stimulatory molecules (such as B7) or inefficient antigen presentation ability. Therefore, potentially tumorreactive T-cells could be induced to mount ineffective
immune responses or even to present anergy.
At advanced stages of carcinogenesis, the immune system exerts a selective pressure on the genetically
unstable tumor cells: those able to resist to or suppress
the immune response are selected. This phenomenon,
known as immunoselection, represents the first cause of
immune escape.
Later in the process of tumor progression, inefficient
immune responses can even favor tumor growth, in a
process known as immunosubversion [39].
This complex sequence of events is known as cancer
immunoediting: effective recognition corresponds to the
elimination of transformed cells, but tumor cell variants
can survive this process and enter an equilibrium phase,
followed by an uncontrolled tumor expansion termed
escape.
It is evident that elimination (firstly described as
“immune surveillance hypothesis” by Burnet M. in 1957
[44] represents a critical factor controlling carcinogenesis, and that immunosenescence plays an essential role
in promoting cancer immunoediting.
Cellular senescence
Combined mechanisms are responsible of cellular senescence in vivo. It has been hypothesized that aging could
be the result of the progressive addition of molecular
damages, or that could be genetically pre-determined.
A number of evidences support the pre-determination
of cellular senescence. One of the most relevant factors
Mazzola et al. Immunity & Ageing 2012, 9:4
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affecting cell aging is telomere shortening through multiple cell cycles. Accordingly telomerase, a specific
enzyme preserving telomeres length, is poorly expressed
in most human non-dividing cells and its levels decline
with cell aging. Because telomeres protect chromosomal
DNA from damages activating programmed cell death
pathways (apoptosis), their shortening is thought to
function as a “sensor” of cells age [13-23,40]. Perhaps
not surprisingly, tumor cells abnormally express telomerase, which allows the maintenance of telomeres’
length even after repeated replications. This potentially
results in tumor “immortality”. Other cellular senescence-related mechanisms are telomere-independent.
Environmental modifications (e.g. increments of oxygen
concentration and free oxygen radicals, DNA damage)
can induce the aging process independently from telomere length [41-43].
In conclusion, cellular senescence is a genetically
determined process that can also be induced by various
alterations in the tumor environment. Studies on
advanced cancer disease have rarely demonstrated the
presence of senescent cellular phenotypes [45,46].
Furthermore, inflammation has also been shown as a
promoter cellular senescence. Still too many interactions
remain to be clarified, considering that the accelerated
aging phenotype has also been evidenced in other diseases, e.g. in atherosclerosis, COPD [47] and liver fibrosis [48].
Inflammaging
Not only adaptive responses, but also innate immune
system is dysregulated during the senescence. The term
“inflammaging” has been coined in 2000 by Franceschi
C. et al. [35] to describe the phenomenon, triggered by
the unspecific innate immunity, of chronic low-grade
systemic inflammation which accompanies the aging
process. Moreover, this condition represents a “common
soil” for different age-associated chronic diseases, such
as diabetes, atherosclerosis, Alzheimer’s disease [32,35],
arthrosis/arthritis, cardiovascular diseases, and cancer
[32].
The association between chronic inflammation and
cancer has been widely described in different organs:
inflammatory bowel diseases (IBDs) determine an
increased incidence of colorectal cancer, while chronic
gastritis is associated with gastric adenocarcinoma, and
chronic viral hepatitis often leads to liver cancer. Various mechanisms account for inflammation-related carcinogenesis (Figure 1).
1. inflammatory leukocytes generate reactive oxygen
and nitrogen species (ROS and RNS, respectively), causing local tissue alterations and DNA damage
Page 3 of 11
2. enhanced proliferative signals mediated by cytokines
released by inflammatory cells increase the risk of
mutations
3. alterations in epigenetic mechanisms alter gene
expression patterns
4. inflammatory mediators affect suppressor cell populations, particularly MDSCs and T-regulatory (Treg)
cells, able to inhibit CD4+ and CD8+ T-cell proliferation,
to block NK cell activation, to limit DC maturation, and
to polarize immunity towards a type-2 helper response
5. the inflammatory microenvironment favors tumorassociated angiogenesis
6. cytokines generate a preferential niche supporting
cancer stem cells (e.g. IL-4 for colon carcinoma stem
cells).
In this scenario, where a number of alterations involve
multiple cellular mechanisms, there is a growing need to
identify one or a few target molecules shared by all cancer cells, in order to synthesize new and more efficient
treatments. One of the mechanisms that could be targeted for this purpose is represented by telomere shortening/elongation.
The importance of telomerase
Telomeres maintain chromosomal stability through
repeated cellular divisions. Their repeated sequence of
non-coding DNA (TTAGGG) has the crucial function
to preserve genomic information during cell replication,
but it results in progressive telomere shortening. Once
the limiting length is reached, signaling of chromosomal
instability triggers cellular senescence and apoptosis,
unless the cell has the ability to preserve telomere
length.
The enzyme telomerase is a reverse transcriptase
responsible for the maintenance of telomeres length.
Since telomerase discovery in 1984 by C.W. Greider and
E. Blackburn, it represented an attractive therapeutic
target because of its role in aging and cancer. Telomerase has recently gained attention for its potential applications in cancer therapy, anti-aging research and
treatment of chronic diseases.
Telomerase expression makes cells potentially
“immortal”, including cancer stem cells. Accordingly, telomerase has been found in a variety of human cancers
(80-90%), a condition that satisfies the need for a tumor
specific target and could define this enzyme as a hallmark of cancer disease because telomerase activity also
is poorly or non-expressed in normal somatic cells.
Telomerase-based therapies
Different approaches have been tailored to telomerase
synthesis or activity.
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Figure 1 Pro-inflammatory mechanisms probably involved in cancer development and progression at old age.
1. Direct enzyme inhibition, through antagonists of
different components of the macromolecular complex
(such as hTERT or TERC)
2. Active immunotherapy, aiming to stimulate
immune responses against tumor cells expressing
hTERT. For instance, Antigen-Presenting Cells (APCs)
displaying hTERT epitopes, are able to stimulate specific
T-cells to react towards telomerase-expressing tumors,
also activating hTERT-specific memory T-cells
3. Telomere disruption/alteration: blocking or altering
telomere structure (e.g. by using mutant engineered
forms of hTERC) may quickly induce a DNA damage
response and consequent apoptosis. However, this
approach could target telomeres in normal cells or Grich chromosome regions, resulting in potentially lethal
toxicities
4. Delivery of telomerase promoter-controlled suicide
genes, able to induce apoptosis selectively in telomerasepositive cells
5. Blocking telomerase expression or functions would
result in reduced enzyme activity in tumor cells. The
potential disadvantage of these approaches is the need
for prolonged therapies to maintain a clinical response.
Examples of drugs recently under clinical trials are
GRN163, GV1001 and GRNVAC1. The first, from
Geron Corporation™ http://www.geron.com, belongs to
the class of direct telomerase inhibitors blocking the
hTERC. GRN163 intracellular distribution has been
recently improved by lipid conjugation [49]
(GRN163®GRN163L).
GV1001 (GemVax/Pharmexa™) and GRNVAC1
(Geron Corporation™) are two active immunotherapy
options, both able to elicit CD8 + and CD4 + T-cell
responses. GV1001 is a hTERT peptide activating CD8+
T cells (through MHC class I). GRNVAC1 consists in
autologous DCs transduced with TERT-LAMP encoding
mRNA. LAMP (lysosomal-associated membrane protein)
favours lysosomal processing and presentation on MHC
class II).
Vaccine strategies in the elderly
Adoptive vaccination seems the most promising strategy
to improve cancer vaccines in the geriatric population.
It consists of transferring immunity through the administration of specific antibodies or immune cells, such as
T-cells [50-52] or DCs [53]. DCs are the most relevant
Mazzola et al. Immunity & Ageing 2012, 9:4
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cellular determinants of vaccine-induced immunity
through adaptive responses, but DC-mediated reaction
is linked with innate immunity, since the induced antibody response activates the complement cascade
[5-23,44,54-57].
However, even DC populations undergo important
changes with advancing age.
Aging and dendritic cells
Lots of studies have been conducted on animal models
and in humans, demonstrating the decrease of DCs in
number, distribution, and potentially, their generation
and development from hematopoietic precursors
[5-23,44,53,55-57]. Other observations showed that
human thymic DCs decline in number (because of
reduced thymic cellularity) but not in proportion in
respect to young individuals [50-53]. Epidermal Langerhans Cells (LC), a skin and conjunctival subtype of DCs,
also decrease in number with age and UV exposure,
playing a permissive role in the development of skin
cancers in the aged or sun-damaged skin
[5-23,44,50-58]. In human blood, peripheral DCs are
identified in two subsets: DC1, expressing CD11c and
called “myeloid” (mDC), and DC2, expressing CD123
and called “plasmacytoid” (pDC). Teig N. et al. [53]
revealed that CD11c + DC1 subpopulation did not
change in the elderly, while CD123+ DC2 decreased.
In vitro studies found that DCs from young and old
subjects expressed the same molecular patterns on their
surface. Furthermore, DCs generated in vitro from
elderly donors survived better under culture conditions.
DCs from different healthy individuals were also equally
effective with age in stimulating T cell responsiveness in
vitro [50-54,58]. However, in vivo studies showed that
DCs in elderly individuals are less able to stimulate
immune responses. Finally, a comparison with DCs generated ex vivo from precursor cells evidenced their complete functionality; it seems that DC precursors are still
able to differentiate into functionally active DCs in the
elderly, with an appropriate stimulation. This was an
evident and attractive potential target for therapeutic
approaches in age-associated malfunctions of the
immune system [5-23,44,50-58]. The problem is that
unhealthy elderly patients, e.g. with cancer disease, may
present with multiple impairments, both in T-cell
responses and in APCs functions [5-23,44,50-58].
Further investigations are necessary to clarify the activation and differentiation signaling, to improve DC functionality when altered, and increase vaccine efficacy in
the elderly.
DC-based vaccines
In order to stimulate tumor-specific CTLs [58], DC vaccines may be performed by using:
Page 5 of 11
1. whole tumor lysates
2. viral, bacterial or yeast vectors
3. specific proteins/peptides
4. nucleic acids
Autologous or allogenic tumor cells can be modified
and administered in association with adjuvants or as
tumor-cell lysates. The advantage of this method is the
possibility that multiple and still unknown antigens can
be simultaneously targeted. Moreover, whole tumor cell
vaccines elicit MHC-I and -II responses. On the contrary, unfavorable aspects include a probability that
unknown weak TAAs may trigger auto-immune
responses.
Vectors are the more immunogenic way to deliver
recombinant genes into DCs, which are better than
direct administration with adjuvants. Issues include the
choice of an efficient vector, and a balance between the
stimulation of innate versus adaptive responses.
Proteins can be administered as single agents, in combinations, or as fusion proteins, and also peptides as single agents, agonist peptides, and anti-idiotype antibodies.
Advantages include cost-effective production, storage,
and distribution. The identification and administration
of TSAs is more accurate, leading to a low risk of inducing auto-immunity respect to tumor cells. On the other
hand, single proteins or peptides are weakly immunogenic, and tumor antigen mutations or loss can easily
escape immune recognition. Another disadvantage is
represented by HLA-restricted responses that limit their
use to selected patients. Finally, their poor ability to
induce balanced activation of CD4+ CD8+ subsets leads
to a less effective long-term anti-tumor immunity.
The consecutive administration of different TSAs, in
different time points, has shown better outcomes than
the simultaneous one.
DNA-based vaccines are a strategy capable of activating strong immunity against weak TAAs.
Approaches to enhance their potency include
improved delivery systems, co-administration of cytokines, or the use of separate plasmids encoding nonself antigens; mRNA vaccines are based on transient
transfection of non-dividing cells: the transfected
mRNA does not integrate into the host genome [59],
determining an high grade of safety. Further transfection efficiency may be obtained by a procedure called
electroporation [60]. The rationale of these vaccines is
the translation into protein of mRNA-coding TAA
transfected into DCs; then, after protein processing,
the synthesized antigen is loaded on MHC molecules
for antigen presentation, activating an antigen-specific
CTL-response [61,74-77].
However, triggering the immune response alone seems
to be an incomplete strategy of vaccination because of
multiple cited factors harming the immune system.
Mazzola et al. Immunity & Ageing 2012, 9:4
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Page 6 of 11
Assessment of elderly patients with cancer
The heterogeneity of the elderly makes managing the
older patient with cancer very challenging. Chronological age does not correlate with better response or
increased toxicity to treatment. There are no known criteria to help decide management plan as older adults
are underrepresented in oncology clinical trials that set
the standard of care. The Comprehensive Geriatric
assessment (CGA) has been suggested as a tool to evaluate elderly patients with cancer. It includes multidimensional assessments, including comorbidities, functional
status, cognition, psychological state, nutrition, social
conditions and medications. This provides a detailed
assessment of the patient which helps to individualize
management. Malnutrition and functional statuses were
found to independently predict change in cancer management especially in the vulnerable elderly [56].
Cancer therapy in the elderly
The flow-chart highlights the different possibilities of
treatment administration and association, focusing on
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cancer vaccination handiness, independently from disease staging and treatment purpose.
When the risk of morbidity and mortality from neoplastic disease is low considering life expectancy and
severity of co-morbidities, the choice should be palliation, including:
• Management of co-morbidities
• Symptomatic approaches (control of pain and cancer-related symptoms)
• Supportive medical and psycho-social care.
If the estimate of life expectancy and the assessment
of co-morbidities and functional status determine a
moderate to high risk of morbidity and mortality from
cancer during the lifespan, then a complete clinical and
psycho-social evaluation should be performed in order
to estimate a realistic risk/benefit ratio (Figure 2).
Apart from the patient’s underlying medical characteristics and the number of conditions affecting the
immune system during cancer disease, the true risk factors for a cancer therapy are represented by its inefficacy
and side effects (Figure 3).
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Figure 2 The importance of estimating life expectancy and comorbidities, in association with the Comprehensive Geriatric
Assessment, in order to guide cancer therapy in the elderly. Independently from the intent, the maintenance of Quality of Life and the
control of cancer-related symptoms should be the first aim of the treatment.
Mazzola et al. Immunity & Ageing 2012, 9:4
http://www.immunityageing.com/content/9/1/4
Page 7 of 11
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Figure 3 Potential risks and benefits of cancer therapy in the elderly.
If risk/benefit ratio is acceptable, conventional curative
options include surgery, radiation therapy and chemotherapy, usually dose-adjusted (Figures 4 and 5).
Surgical approaches may represent the first option for
solid tumors; elective surgery in the elderly cancer
patients, and in the geriatric population in general
[62,73], have shown similar outcomes as in the younger
ones [63]. This consideration warrants performing a
CGA and preoperative assessment is required [64]. Geriatric surgery is about disease and functional status, not
age. Early mobilization and rehabilitation after surgery
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Figure 4 Possible decisional algorithm for cancer therapy in
the elderly, from screening to treatment, Step 1-2.
were shown to reduce the incidence of post-operative
complications. In association with this option, cancer
vaccination could find application both in neo-adjuvant
and adjuvant strategies, co-administered with Radiation
Therapy (RT) or CT.
Both brachytherapy and external beam source can be
proposed either in the curative or palliative setting. RT
is usually effective and well tolerated. However standard
protocols and/or doses sometimes need to be modified
according to patient’s conditions or to the onset of complications [65]. As for surgery, age per se does not
represent a limiting factor to the prescription of RT
[66,67].
Chemotherapy may be considered as a first-line
approach, as well as an adjuvant in combination with
RT, or as palliative treatment. In any case, it should
always be individualized in the elderly. Clinical trials
have focused mainly on young and adult populations,
and in a few cases, on a selected, much healthier population of “young old” (65-75 years old) or “old” patients
(76-85 years old). However, only a relatively small percentage of the geriatric population is actually fit and
capable of tolerating standard dose CT regimens [68].
The increased incidence and prevalence of multiple comorbidities, their severity, and the presence of functional impairment (measured by the means of ADL
scale), act as potential additional risk factors or contraindications involving dose/schedule adjustments or drug
Mazzola et al. Immunity & Ageing 2012, 9:4
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Page 8 of 11
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Figure 5 Possible decisional algorithm for cancer therapy in the elderly, Step 3. The entire flow-chart enlightens the possibilities of
administration and association of cancer vaccines at different steps of the evaluation of malignancies, from prevention to curative and palliative
treatments.
substitution at baseline. Patients with poor functional
statuses, decreased social activities, and poor hearing
were found to be at increased risk of chemotherapy
toxicity [57], Moreover, once CT is established, it is also
affected by an high incidence of multiple side effects:
hydration and electrolyte imbalances, gastrointestinal
effects (nausea, vomiting, diarrhea) and consequences
(malnutrition), infections (with or without leucopenia),
functional decadence and dependence, delirium and/or
accelerated cognitive dysfunction, myelosuppression
(causing anemia, thrombocytopenia, neutropenia),
mucositis, organ-specific toxicity (cardiac, renal), sense
organ deficits (hearing-visual impairment), peripheral
and/or central neurotoxicity. All these factors contribute
to the eventual discontinuation of CT, adjusted doses or
a change in the regimen used. A number of studies have
been performed in order to decrease, prevent, and treat
these conditions. Several recommendations produced in
recent years resulted in a better control of CT-related
complications, but these conditions remained serious
problems, sometimes refractory to all kinds of treatments. Comprehensive supportive care (aggressive
intravenous rehydration, nutritional and vitamin supplements, prophylactic hematopoietic growth factors
[69-71], blood transfusions, iron therapy, organ-specific
monitoring [72,73], hospitalization if necessary) is therefore crucial throughout the CT course.
“Targeted therapies” represent a recent therapeutic
pharmacological option for a number of malignancies,
and are based on the concept that molecular changes
responsible for malignant transformation can be targeted by specific agents. The aim of these treatments is
to discriminate cancer cells, reducing adverse effects on
healthy cells and improving overall benefits. This option
captured increasing interest in geriatric cancer patients’
care, yet beneficial and adverse effects should be further
analyzed in this segment of the population, also for
those patients who are unable to tolerate cytoreductive
CT. Once more, cancer vaccination could be associated
with this option or also administered alone in this group
of patients.
However, inclusion of the elderly (fit and unfit individuals) in cancer vaccine clinical trials is warranted, and
a careful selection of patients who would benefit from
Mazzola et al. Immunity & Ageing 2012, 9:4
http://www.immunityageing.com/content/9/1/4
this treatment is critical [5-23,44,55-57]. Biological drugs
can also be used in association with RT, CT, or both,
only after an accurate re-evaluation of the risk/benefit
ratio because of the important reported side effects
[37,55].
Conclusion
Cancer prevention remains critical in the geriatric, as
well as in the young population [5-23,44,55-57].
The development and use of cancer vaccines also
should be widely encouraged [5-23,44,55-57]. The
immune system in elderly cancer patients is weakened
by age-related changes and usually by the immunosuppressive effects of conventional treatments: this condition may suggest the use of cancer vaccination
approaches before or together with other treatments. In
any case, to identify and understand which alterations
occur in the senescent immune system is the only way
for individualizing, optimising and enhancing the antitumor immune responses in the geriatric population.
Although further and great improvements in cancer vaccines are warranted, at present this approach should be
suggested in association with systematic cancer prevention and conventional therapies (surgery, chemotherapy,
radiation therapy). When cancer is involved, both in the
young and in the elderly population, the strategy should
be: “treat early, treat often”.
Abbreviations
CGA: Comprehensive Geriatric Assessment; IBD: Inflammatory Bowel Disease;
MDSC: Myeloid-Derived Suppressor Cell; QOL: quality of life; TAA: TumorAssociated Antigen; TCR: T-Cell Receptor; TSA: Tumor-Specific Antigen; TNF:
Tumor Necrosis Factor.
Acknowledgements
We thank Marjorie Jenkins, Executive Director of the Laura W. Bush Institute
for Women’s Health, the Billy and Ruby Power Family and Everardo Cobos,
Associate Dean of the Oncology Programs at TTUHSC. We thank Teri Fields
for her assistance in editing this manuscript.
Funding
This project was supported by the Billy and Ruby Power Endowment for
Cancer Research and Laura W. Bush Institute for Women’s Health and Center
for Women’s Health and Gender-Based Medicine. The Division of
Hematology/Oncology and the office of the Associate Dean of the
Oncology Programs at TTUHSC.
Author details
Department of Clinical and Preventive Medicine, University of MilanoBicocca, Geriatric Clinic, San Gerardo University Hospital, Monza, Italy.
2
Department of Internal Medicine, Division of Hematology/Oncology, Texas
Tech University Health Sciences Center, 3601 4th St, Lubbock, TX 79430,
USA. 3Department of Medicine, Surgery and Dentistry, Università degli Studi
di Milano, Milan, Italy. 4The Laura W. Bush Institute for Women’s Health and
Center for Women’s Health and Gender-Based Medicine, Texas Tech
University Health Sciences Center, Amarillo, TX, USA.
1
Authors’ contributions
PM, LM, SR, MCI and EC reviewed the current literature. PM wrote the
manuscript and MCI, GA, SR, LM, EC, MJ revised the manuscript. MCI
conceived and drafted the manuscript. MCI, EC, GA approved the final
version.
Page 9 of 11
Competing interests
The authors declare that they have no competing interests.
Received: 11 October 2011 Accepted: 17 April 2012
Published: 17 April 2012
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doi:10.1186/1742-4933-9-4
Cite this article as: Mazzola et al.: Aging, cancer, and cancer vaccines.
Immunity & Ageing 2012 9:4.
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