world cancer report - iarc
world cancer report - iarc
world cancer report - iarc
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- Interference with B-cell function;<br />
- Interference with proliferation; clonal<br />
expansion (cyclophosphamide, methotrexate).<br />
Organ transplant recipients receiving<br />
immunosuppressive drugs are at<br />
increased risk of non-Hodgkin lymphoma<br />
and some other <strong>cancer</strong>s, especially nonmelanoma<br />
skin <strong>cancer</strong> and Kaposi sarcoma<br />
(Table 2.19). Some such tumour types<br />
exemplify the manner in which immunosuppression<br />
has been otherwise linked to<br />
malignancy. Thus, a factor in the development<br />
of skin <strong>cancer</strong> is the ability of ultraviolet<br />
B radiation to suppress the immune<br />
response. Such immunomodulation may<br />
be by multiple mechanisms but generally<br />
manifests in an antigen-presenting cell<br />
defect and an altered cytokine environment<br />
in the draining lymph nodes [3].<br />
Consistent with a role of immunosuppression<br />
in the etiology of these tumours,<br />
immunosuppression profoundly influences<br />
the prevalence of skin disorders in<br />
transplant patients: skin tumours occur<br />
with high incidence in such patients and<br />
constitute a major part of transplantation-related<br />
morbidity and mortality. On<br />
the other hand, evidence of immune system<br />
abnormalities is lacking in most<br />
patients with mature B-cell neoplasms.<br />
Nonetheless, immunosuppressed<br />
patients have a markedly increased incidence<br />
of such non-Hodgkin lymphoma<br />
[4].<br />
More than 95% of all human beings are<br />
infected with the oncogenic herpesvirus,<br />
Epstein-Barr virus (EBV), which rarely<br />
causes clinically apparent disease except<br />
in immunocompromised individuals,<br />
including organ transplant recipients.<br />
Epstein-Barr virus-associated lymphoproliferative<br />
diseases in immunocompromised<br />
patients include a spectrum of<br />
mainly B-cell diseases that range from<br />
polyclonal lymphoproliferative diseases,<br />
which resolve when immunosuppression<br />
is halted, to highly malignant lymphomas<br />
[5]. EBV transforms lymphoid cells and the<br />
neoplastic cells can survive and proliferate<br />
to produce lymphomas very rapidly in<br />
an immunocompromised individual [6].<br />
Because of the synergistic effects of EBV<br />
and immunosuppressive drugs in the cau-<br />
sation of these lymphomas, both EBV and<br />
some of the drugs listed in Table 2.19 are<br />
classified in Group 1 (carcinogenic to<br />
humans) by the IARC Monographs on the<br />
Evaluation of Carcinogenic Risks to<br />
Humans. Cancers of the anogenital region<br />
are caused by infections with human<br />
papillomaviruses, and the incidence of<br />
such <strong>cancer</strong>s is greatly increased in organ<br />
transplant recipients.<br />
Autoimmune conditions for which<br />
immunosuppressive therapy is indicated<br />
include rheumatoid arthritis and lupus<br />
erythematosis and others. Milder therapy<br />
and, often, less potently immunosuppressive<br />
drugs (e.g. steroids such as prednisone)<br />
are generally used than for organ<br />
transplant recipients. Generally there are<br />
elevated risks for the same <strong>cancer</strong>s as<br />
occur in excess in organ transplant recipients,<br />
but these risks are much lower in<br />
patients without an organ transplant.<br />
Prednisone and related immunosuppressive<br />
steroid drugs have not been shown to<br />
be carcinogenic.<br />
Immunosuppression that will allow transplanted<br />
normal tissues to survive in a foreign<br />
host can also allow occult tumours within<br />
the transplanted tissues to survive and grow<br />
in the transplant recipient. Such transplanted<br />
<strong>cancer</strong>s regress when immunosuppressive<br />
therapy is withdrawn [7].<br />
Immunosuppression by carcinogens<br />
As implied by the number of malignancies<br />
which emerge once the immune system is<br />
compromised, growth of tumours generally<br />
may be perceived as requiring a<br />
degree of failure by the immune<br />
response. Generally, chemical carcinogens<br />
are not characterized as immunotoxic.<br />
However, particular substances may<br />
exert some degree of immunosuppressive<br />
activity that may thus affect tumour<br />
growth in a manner comparable to that<br />
exerted by ultraviolet light in the etiology<br />
of skin <strong>cancer</strong> [2]. Thus TCDD (2,3,7,8tetrachlorodibenzo-para-dioxin)<br />
is<br />
immunotoxic in primates, suggesting that<br />
humans exposed to this pollutant may be<br />
similarly affected, although no direct evidence<br />
was found to support this in a<br />
study of exposed residents living in a contaminated<br />
area in Seveso, Italy.<br />
Fig. 2.60 Transport of an organ for transplantation.<br />
Immunosuppressed transplant patients exhibit an<br />
increased incidence of tumours, particularly<br />
lymphomas.<br />
Fig. 2.61 An Epstein-Barr virus-positive, diffuse large<br />
B-cell lymphoma of soft tissue, arising in a patient<br />
with rheumatoid arthritis treated with methotrexate.<br />
Fig. 2.62 A liver biopsy showing partial replacement<br />
of hepatocytes by diffuse large B-cell lymphoma of<br />
the immunoblastic variant, a lymphoproliferative disease<br />
which arose after organ transplant.<br />
Fig. 2.63 Bone marrow smear of an acute myeloid<br />
leukaemia arising in a <strong>cancer</strong> patient treated with<br />
alkylating agents. Note the increased numbers of<br />
basophils.<br />
Immunosuppression<br />
69