Immunosuppression cancer associated with

Corticotropin is used for diagnostic testing of adrenocortical function. This drug may also be used for the management of acute exacerbations of multiple sclerosis, nonsuppurative thyroiditis, and hypercalcemia associated with cancer. It is also used as an anti-inflammatory and immunosuppressant drug when conventional glucocorticoid therapy lias not been effective (see Display 50-1). 

Prevention Minimize immunosuppressant doses avoid sun exposure (sunblock, hats, clothing) routine self-exams (skin, lymph nodes) yearly gynecologic/prostate exams AZA particularly associated with skin cancers CSA/TAC may be associated with lymphoproliferative disorders (lymphomas)... 

Immunodeficiency has been associated with an increased incidence of viral-induced cancers, which tend to be more immunogenic than those that are chemically-induced. Cancers related to immunosuppression include leukemia and cancers of the skin (seen in transplant patients4) as well as Kaposi s sarcoma and EB V-associated B cell lymphomas (observed in HIV/AIDS patients). 

Chronic infections such as HIV result in immunosuppression as a result of induction of CD4+ Treg cells. Increased risk of Kaposi s sarcoma, non-Hodgkin s lymphoma and liver cancer is associated with long-term infections such as HIV. Immunosuppression in HIV-infected individuals occurs before the development of AIDS, which proceeds before the depletion of CD4+ T cells, and the induction of Treg cells may play a role in this process. The mechanisms are IL-10-independent and include the involvement of TGF-(3 secreted via signaling through cell-cell interaction involving CTLA-4. 

The precise role of immunological surveillance in tumorigenesis is not well dehned for the majority of malignancies. The occurrence of a unique spectrum of malignancies in immunosuppressed individuals suggests either that immune surveillance is only important in certain tumors or that the duration needed to see an increased incidence of many more common tumors (e.g., colorectal, breast, lung, or prostate carcinomas) is not reached. Suppression of T cell mediated immunity has, however, been unequivocally associated with an increased incidence of certain mahgnancies. In patients with profound defects in T cell immunity the time to tumor detection is often shorter than for cancers induced by other mechanisms. 

Anticancer chemotherapies Azathioprine, cyclophosphamide, methotrexate etc. The cytotoxic substances affect proliferating cells and hematopoiesis as well as lymphocyte proliferation are especially sensitive. Association with risk of clinical infections clearly established. 1 % of chemotherapy patients develop an independent cancer within 10 years, 3 % within 20. Noteworthy, some anticancer drugs are now used also as immunosuppressant for autoimmune diseases... 

Immunosuppressants such as azathioprine and mercaptopurine have a significant potential for adverse reactions. Azathioprine causes bone marrow suppression and has been associated with lymphomas (in renal transplant patients), skin cancer, and pancreatitis (about 3% of patients). Some investigators believe that induction of leukopenia may be necessary for therapeutic effect. Mercaptopurine causes adverse reactions similarly to azathioprine however, there are fewer reports of lymphomas with this agent. In one cohort of IBD patients, adverse effects from mercaptopurine were as follows pancreatitis, 1.2% allergic reactions, 3.9%, significant leukopenia, 11.5% and infectious complications, 14%. Ten percent of patients who received azathioprine or mercaptopurine required discontinuation of treatment because of adverse effects. Allopurinol inhibits the metabolism of mercaptopurine, and a dosage reduction of the latter is required when the two are used in combination. 

Prevention Minimize immunosuppressant doses avoid sun AZA particularly associated with skin cancers... 

Cancer. In cancer patients it is hoped that thymic factors can be employed as adjuncts to conventional chemotherapy or radiation therapy to ameliorate the immunosuppressive side effects associated with such treatment. If T cell-dependent immunity were maintained and/or restored, the cancer patient would theoretically be more capable of mounting a specific host immune response against the tumor, as well as to the various viral, bacterial, and fungal pathogens to which he would otherwise be susceptible. 

Few experimental carcinogens of the epigenetic type have been associated with cancer in humans, these are mainly hormones or immunosuppressants. Humans have been exposed to many pesticides known to cause cancer in experimental animals, but none has been linked to cancer in humans (38). The absence of effects in humans has been suggested to be due the fact that exposures of humans are below the threshold for the biological effect (e.g. peroxisome proliferation or membrane alteration and consequent promoting action) underlying carcinogenicity (36). Moreover, some of the conditions necessary for tumor Induction in rodents may not be attainable or tolerable to humans. 

The immune system plays a major role in protecting the host from infectious disease and, arguably, from cancer. This is demonstrated by the association between the therapeutic use of chemical immunosuppressants (i.e., in cancer chemotherapy or organ transplantation) and an increased incidence of infections (1) and certain cancers (2). This relationship is also illustrated by the Acquired Immune Deficiency Syndrome (AIDS), in which a loss of immune responsiveness is associated with infection with Pneumocysti s carinii and other... 

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