IMMUNE-RESPONSE AGAINST MEDULLARY-THYROID CARCINOMA (MTC) INDUCED BY PARENTAL AND OR INTERLEUKIN-2-SECRETING MTC CELLS IN A RAT MODEL OF HUMAN FAMILIAL MEDULLARY-THYROID CARCINOMA/

The existence of inherited aggressive forms of medullary thyroid carci noma (MTC), and their resistance to all classical therapies, make it a prime candidate for adoptive immunotherapy. As a prelude to a vaccine for the protection of family members at risk of developing the diseas e, we investigated the immunological antitumour response provoked by t he 6/23 rMTC cell line, compared to that of the same cells engineered to secrete interleukin-2 (rMTC-IL2), in an animal model of familial hu man MTC, the inbred strain of Wag/Rij rats. The rMTC cells developed a tumour that invaded the whole neck 15 days after orthotopic injection (into the thyroid), while the rMTC-IL2 cells were progressively rejec ted. Co-injection of rMTC-IL2 with the parental cells induced the reje ction of the rMTC transplants. When injected, both tumoral cell types showed a similar positive immunoreaction with anti-MHC class I (major histocompatibility complex class I) antibodies. They both recruited na tural killer cells and eosinophils at the side of injection. In additi on, CD8(+) T lymphocytes infiltrated the rMTC-IL2 cells, macrophages a nd CD4(+) T lymphocytes were scarce. Our results suggest that the CD8( +) T lymphocytes are implicated in the anti-tumour reaction elicited b y the IL-2-transfected cells. As these effectors are known to induce a specific immunological response, including memory, such a protocol sh ould be tested as a vaccine on the young population genetically at ris k of developing a MTC.