world cancer report - iarc

- Interference with B-cell function;
- Interference with proliferation; clonal
expansion (cyclophosphamide, methotrexate).
Organ transplant recipients receiving
immunosuppressive drugs are at
increased risk of non-Hodgkin lymphoma
and some other cancers, especially nonmelanoma
skin cancer and Kaposi sarcoma
(Table 2.19). Some such tumour types
exemplify the manner in which immunosuppression
has been otherwise linked to
malignancy. Thus, a factor in the development
of skin cancer is the ability of ultraviolet
B radiation to suppress the immune
response. Such immunomodulation may
be by multiple mechanisms but generally
manifests in an antigen-presenting cell
defect and an altered cytokine environment
in the draining lymph nodes [3].
Consistent with a role of immunosuppression
in the etiology of these tumours,
immunosuppression profoundly influences
the prevalence of skin disorders in
transplant patients: skin tumours occur
with high incidence in such patients and
constitute a major part of transplantation-related
morbidity and mortality. On
the other hand, evidence of immune system
abnormalities is lacking in most
patients with mature B-cell neoplasms.
Nonetheless, immunosuppressed
patients have a markedly increased incidence
of such non-Hodgkin lymphoma
[4].
More than 95% of all human beings are
infected with the oncogenic herpesvirus,
Epstein-Barr virus (EBV), which rarely
causes clinically apparent disease except
in immunocompromised individuals,
including organ transplant recipients.
Epstein-Barr virus-associated lymphoproliferative
diseases in immunocompromised
patients include a spectrum of
mainly B-cell diseases that range from
polyclonal lymphoproliferative diseases,
which resolve when immunosuppression
is halted, to highly malignant lymphomas
[5]. EBV transforms lymphoid cells and the
neoplastic cells can survive and proliferate
to produce lymphomas very rapidly in
an immunocompromised individual [6].
Because of the synergistic effects of EBV
and immunosuppressive drugs in the cau-
sation of these lymphomas, both EBV and
some of the drugs listed in Table 2.19 are
classified in Group 1 (carcinogenic to
humans) by the IARC Monographs on the
Evaluation of Carcinogenic Risks to
Humans. Cancers of the anogenital region
are caused by infections with human
papillomaviruses, and the incidence of
such cancers is greatly increased in organ
transplant recipients.
Autoimmune conditions for which
immunosuppressive therapy is indicated
include rheumatoid arthritis and lupus
erythematosis and others. Milder therapy
and, often, less potently immunosuppressive
drugs (e.g. steroids such as prednisone)
are generally used than for organ
transplant recipients. Generally there are
elevated risks for the same cancers as
occur in excess in organ transplant recipients,
but these risks are much lower in
patients without an organ transplant.
Prednisone and related immunosuppressive
steroid drugs have not been shown to
be carcinogenic.
Immunosuppression that will allow transplanted
normal tissues to survive in a foreign
host can also allow occult tumours within
the transplanted tissues to survive and grow
in the transplant recipient. Such transplanted
cancers regress when immunosuppressive
therapy is withdrawn [7].
Immunosuppression by carcinogens
As implied by the number of malignancies
which emerge once the immune system is
compromised, growth of tumours generally
may be perceived as requiring a
degree of failure by the immune
response. Generally, chemical carcinogens
are not characterized as immunotoxic.
However, particular substances may
exert some degree of immunosuppressive
activity that may thus affect tumour
growth in a manner comparable to that
exerted by ultraviolet light in the etiology
of skin cancer [2]. Thus TCDD (2,3,7,8tetrachlorodibenzo-para-dioxin)
is
immunotoxic in primates, suggesting that
humans exposed to this pollutant may be
similarly affected, although no direct evidence
was found to support this in a
study of exposed residents living in a contaminated
area in Seveso, Italy.
Fig. 2.60 Transport of an organ for transplantation.
Immunosuppressed transplant patients exhibit an
increased incidence of tumours, particularly
lymphomas.
Fig. 2.61 An Epstein-Barr virus-positive, diffuse large
B-cell lymphoma of soft tissue, arising in a patient
with rheumatoid arthritis treated with methotrexate.
Fig. 2.62 A liver biopsy showing partial replacement
of hepatocytes by diffuse large B-cell lymphoma of
the immunoblastic variant, a lymphoproliferative disease
which arose after organ transplant.
Fig. 2.63 Bone marrow smear of an acute myeloid
leukaemia arising in a cancer patient treated with
alkylating agents. Note the increased numbers of
basophils.
Immunosuppression
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