Lymphocytic profiling in thyroid cancer provides clues for failure of tumor immunity.
Thyroid cancers are usually surrounded by a significant number of immune-reactive cells. Tumor-associated lymphocytes as well as background lymphocytic thyroiditis are frequently mentioned in pathology reports of patients who have undergone surgery for thyroid cancer. The nature of this lymphocytic reaction is not well understood. The fact that cancer can survive in this adverse microenvironment is indicative of immune regulation. We characterized the lymphocytic infiltration that accompanies thyroid cancer and compared it with that present in thyroid autoimmunity. We found that double-negative (DN) T cells were significantly more abundant in thyroid cancer than in thyroid autoimmunity. Although FOXP3(+) regulatory T cells were also present, DN T cells were the dominant cell type, associated with thyroid cancer. Furthermore, upon stimulation, the DN T cells associated with cancer remained unchanged, while the few (<5%) DN T cells associated with thyroid autoimmunity increased in numbers (>20%). CD25 expression on DN T cells remained unchanged after stimulation, which indicates that the increase in the absolute number of DN T cells in thyroid autoimmunity was at the expense of inactivation of single-positive T cells. We concluded that in the setting of thyroid cancer, DN T cells appear to suppress tumor immunity. In contrast, in thyroid autoimmunity, DN T cells were barely present and only increased at the expense of inactivated, single-positive T cells upon induction. Together, these findings indicate that thyroid cancer-associated DN T cells might regulate proliferation and effector function of T cells and thereby contribute to tumor tolerance and active avoidance of tumor immunity.
['Imam|Shahnawaz|S|', 'Paparodis|Rodis|R|', 'Sharma|Deepak|D|', 'Jaume|Juan Carlos|JC|']
D015551:Autoimmunity D002291:Carcinoma, Papillary D016022:Case-Control Studies D002478:Cells, Cultured D005434:Flow Cytometry D051858:Forkhead Transcription Factors D050031:Hashimoto Disease D006801:Humans D007108:Immune Tolerance D007371:Interferon-gamma D020381:Interleukin-17 D008214:Lymphocytes D050378:T-Lymphocytes, Regulatory D013961:Thyroid Gland D013964:Thyroid Neoplasms
thyroid cancer tumor immunity autoimmunity Hashimoto thyroiditis