world cancer report - iarc

IMMUNOSUPPRESSION
SUMMARY
>Persistent suppression of the immune
system results in an increased cancer
risk.
> An increased incidence of malignant
lymphomas, of which the majority contain
the Epstein-Barr virus, is caused by
immunosuppressive drugs used to prevent
the rejection of organ transplants.
> Infectious agents that cause severe
immune suppression, such as the
human immunodeficiency virus (HIV),
are associated with an increased incidence
of several tumours, including non-
Hodgkin lymphoma and Kaposi sarcoma.
Immunosuppression is a reduction in the
capacity of the immune system to respond
effectively to foreign antigens, and can be
either transient or permanent.
Certain chemicals and drugs, ionizing radiation,
and infection with particular viruses
and parasites can cause immunosuppression.
This phenomenon is observed in
humans and in experimental animals.
Immunosuppression after exposure to Xrays
or other ionizing radiation is most pronounced
when the entire body, rather than
a limited area, is irradiated.
Immunosuppression by chemicals or radiation
is dose-dependent, the intensity and
duration of the effect increasing with
increasing dose or continuing exposure,
and is generally reversible with cessation
of exposure. In contrast, infection with certain
pathogens, such as human immunodeficiency
virus, is persistent and the
immune deficiency that results is progressive,
unless the infection is effectively
treated.
Immunosuppression should be distinguished
from various forms of immune
deficiency resulting from certain genetic
defects (e.g. ataxia telangiectasia, ATM;
Wiskott-Aldrich Syndrome, WASP; X-linked
68 The causes of cancer
severe combined immunodeficiency, γc).
Persistent immunosuppression, especially
when accompanied by continuing exposure
to foreign antigens such as organ
transplants, presents a risk for cancer,
though not all tumour types arise with
equal frequency. Ciclosporin and related
compounds are widely used to facilitate
organ transplantation by decreasing the
risk of rejection. Risk is especially high for
various forms of lymphoma and for certain
other cancers that are associated with viral
infections.
Immunosuppression mediated by
drugs
Immunosuppression achieved by administration
of drugs is used to treat autoimmune
diseases (e.g. rheumatoid arthritis)
and, usually involving the relevant drugs at
much higher dosage, to maintain the functional
and anatomic integrity of foreign tissues
grafted to another individual. A graft
from any individual except oneself or an
identical twin will provoke an immune reaction
against the grafted tissues, the intensity
of which varies with the degree of antigenic
difference between graft and host. In
Drug or infectious agent Cancer site/cancer
Table 2.19 Immunosuppressive agents associated with development of cancer.
the absence of adequate immunosuppression,
the host will destroy the graft. Whole
organs (e.g. kidney, heart, liver, lung) can
be transplanted with maintenance of function
that may continue for a lifetime when
appropriate levels of immunosuppression
are maintained. The risk of cancer increases
with increasing intensity and duration of
immunosuppression [1].
Apart from deliberate suppression of the
immune response in the context of organ
transplantation, immunosuppression may
arise as a side-effect of some drugs, and
specifically many cytotoxic agents widely
used in cancer chemotherapy. This action
may contribute to the development of “second
cancers”, particularly in children. More
generally, patients receiving cancer
chemotherapy are vulnerable to infectious
disease as a result of their immune system
being compromised.
The suggested mechanisms of action of
immunosuppressive agents [2] include:
- Interference with antigen-presentation
mechanisms;
- Interference with T-cell function; inhibition
of signal transduction or receptor actions
(ciclosporin);
Azathioprine Non-Hodgkin lymphoma, Kaposi sarcoma,
squamous cell carcinoma of the skin, hepatobiliary
cancers, mesenchymal tumours.
Cyclophosphamide Bladder cancer
Ciclosporin Non-Hodgkin lymphoma, Kaposi sarcoma
Human immunodeficiency Non-Hodgkin (B-cell) lymphoma, Kaposi sarcoma
virus-1 (HIV-1) (increased risk by coinfection with herpesvirus 8)
Epstein-Barr virus Burkitt lymphoma (in conjunction with malaria
infection), non-Hodgkin (B-cell) lymphoma in
immunosuppressed patients, Hodgkin disease,
smooth muscle tumours in immunosuppressed
individuals
Human herpesvirus 8 Kaposi sarcoma
Human papillomaviruses Cancers of cervix, vulva and anus