Immunologic Studies on Tumors
Differentiated thyroid cancers contain TG and microsomal (TPO) antigens cross-reacting with antibody to normal thyroid antigens; this fact can be very useful in identifying metastatic deposits (338). Some tumors tend to lose the microsomal (TPO) antigen (339, 340). There is strong evidence that the immune system mounts a defense against the tumors, although an imperfect one. Tumors commonly are infiltrated by lymphocytes, and there is less tendency for nodal metastasis, and a better prognosis, with tumors so involved (341-343). Antibodies to TG and microsomal antigen are more common in cancer patients than in control subjects (344). We have shown, using in vitro assays, that 50% of patients develop immunity to TG, and some react to apparently specific thyroid tumor antigens (345). The tumor antigen is recognized in both autologous and heterologous tumors, and is not present in Graves' disease tissue. Immunization with tumor preparation has been performed, and in a few cases has led to higher in vivo and in vitro reactivity and apparent partial tumor regression (346). Nonspecific immune complexes are found in 10% of patients with differentiated cancers, and specific TG containing complexes are present at low levels in 30% of patients (347). With progress of thyroid cancer, the immune system gradually loses responsivity, as with other tumors (340, 346,347).
In vivo, circulating antibodies to Tg and/or TPO are found in nearly one fourth of the patients, and the anti-TG antibodies cause interference in assay of this substance thus making follow-up of patients difficult.. Their presence seems not to influence the tumor outcome (348, 349). Interestingly, the disappearance of antithyroid autoantibodies during follow-up, correlates with achievement of complete remission, suggesting that elimination of the antigen with successful therapy causes the disappearance of the corresponding auto-antibody. Thus, the conversion from antibody positive to antibody negative may be interpreted as a marker of remission, while the persistence of the antigen may be regarded as indirect evidence of persistent disease.
The fibrosis and amyloid deposits in medullary cancers might suggest a host antitumor response, and indeed antitumor immune reactivity is detectable in vitro in most of these patients (350).
Sometimes autoimmunity may play an adverse role. Graves' disease co-occurs with 4-8% of thyroid cancers, whether by chance or through a true association is uncertain. The occurrence of TSH-like thyroid-stimulating antibodies in such patients could be related to the development or progress of tumors that have receptors recognized by these antibodies. In some reported cases, the thyroid-stimulatory autoantibodies seem clearly to stimulate the growth of the cancer (351-353), but overall, it is not clear that the co-occurrence of Graves' disease causes thyroid tumors to behave more aggressively.
