Cellular Immune Responses in Familial Medullary Thyroid Carcinoma

We studied prospectively 46 members of a kindred with familial medullary thyroid carcinoma to determine the importance of possible cellular immune reactivity to tumor antigen. We evaluated in vitro production of macrophage-migration-inhibitory factor and ³H-thymidine uptake by lymphocytes from patients, family members and normal subjects in response to extracts of medullary thyroid carcinoma and normal thyroid tissue. Lymphocytes from 12 of 18 patients with medullary thyroid carcinoma and four of seven patients with C-cell hyperplasia produced migration inhibitory factor or proliferated (or both) in response to tumor antigen. In contrast, cells from only two of 25 normal subjects and two of nine family members not genetically at risk for medullary thyroid carcinoma made migration inhibitory factor and proliferated to tumor antigen. Of particular interest, lymphocytes from six of 12 clinically normal family members genetically at risk for medullary thyroid carcinoma exhibited cellular immune reactivity to tumor antigen. (N Engl J Med 296:835–838, 1977) Medullary carcinoma of the thyroid gland usually occurs as a familial disease and is inherited as an autosomal dominant trait.¹² Its detection has been greatly facilitated by the measurement of plasma calcitonin concentrations, which are increased in the premalignant or hyperplastic stage.³ Once metastasis has occurred, the clinical course is variable and may be rapidly fatal or relatively benign. The explanation for the variable rate of tumor progression is unclear, since such factors as age at onset, extent of disease and treatment of patients with advanced medullary carcinoma do not appear to influence the outcome.⁴ In addition, the role of.