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 carcinoma (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 disease, we investigated the immunological antitumour response provoked by the 6/23 rMTC cell line, compared to that of the same cell engineered to secrete interleukin-2 (rMTC-IL2), in an animal model of familial human 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 rejected. Co-injection of rMTC-IL2 with the parental cells induced the rejection 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 natural killer cells and eosinophils at the site of injection. In addition, CD8+ T lymphocytes infiltrated the rMTC-IL2 cells, and eosinophil recruitment was amplified. Neutrophils, macrophages and CD4+ T lymphocytes were scarce. Our results suggest that the CD8+ T lymphocytes are implicated in the anti-tumour reaction elicited by the IL-2-transfected cells. As these effectors are known to induce a specific immunological response, including memory, such a protocol should be tested as a vaccine on the young population genetically at risk of developing a MTC.
Lausson
S
S
Laboratoire d'Endocrinologie Cellulaire et Evolution, U. R. A. 1116 CNRS, Université Paris-Sud, Centre d'Orsay, France.
Fournes
B
B
Borrel
C
C
Milhaud
G
G
Treilhou-Lahille
F
F
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018276:Carcinoma, Medullary / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D002455:Cell Division / Q000502:physiology; D004195:Disease Models, Animal; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D006801:Humans; D016219:Immunotherapy, Adoptive; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology; D009368:Neoplasm Transplantation; D051381:Rats; D011919:Rats, Inbred Strains; D013964:Thyroid Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D014162:Transfection; D014407:Tumor Cells, Cultured
D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2