title: Lymphocytic profiling in thyroid cancer provides clues for failure of tumor immunity.
abstract: 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.
authors.affiliation: Endocrine Autoimmunity UnitDivision of Endocrinology, Diabetes and Metabolism, Department of Medicine, School of Medicine and Public HealthVeterans Affairs Medical CenterUniversity of Wisconsin-Madison, 1685 Highland Avenue, MFCB 4163, Madison, Wisconsin 53705, USA.
authors.forename: Shahnawaz
authors.initials: S
authors.lastname: Imam
authors.affiliation: Endocrine Autoimmunity UnitDivision of Endocrinology, Diabetes and Metabolism, Department of Medicine, School of Medicine and Public HealthVeterans Affairs Medical CenterUniversity of Wisconsin-Madison, 1685 Highland Avenue, MFCB 4163, Madison, Wisconsin 53705, USAEndocrine Autoimmunity UnitDivision of Endocrinology, Diabetes and Metabolism, Department of Medicine, School of Medicine and Public HealthVeterans Affairs Medical CenterUniversity of Wisconsin-Madison, 1685 Highland Avenue, MFCB 4163, Madison, Wisconsin 53705, USA.
authors.forename: Rodis
authors.initials: R
authors.lastname: Paparodis
authors.affiliation: Endocrine Autoimmunity UnitDivision of Endocrinology, Diabetes and Metabolism, Department of Medicine, School of Medicine and Public HealthVeterans Affairs Medical CenterUniversity of Wisconsin-Madison, 1685 Highland Avenue, MFCB 4163, Madison, Wisconsin 53705, USA.
authors.forename: Deepak
authors.initials: D
authors.lastname: Sharma
authors.affiliation: Endocrine Autoimmunity UnitDivision of Endocrinology, Diabetes and Metabolism, Department of Medicine, School of Medicine and Public HealthVeterans Affairs Medical CenterUniversity of Wisconsin-Madison, 1685 Highland Avenue, MFCB 4163, Madison, Wisconsin 53705, USAEndocrine Autoimmunity UnitDivision of Endocrinology, Diabetes and Metabolism, Department of Medicine, School of Medicine and Public HealthVeterans Affairs Medical CenterUniversity of Wisconsin-Madison, 1685 Highland Avenue, MFCB 4163, Madison, Wisconsin 53705, USA jcj@medicine.wisc.edu.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Jaume
mesh_terms: D015551:Autoimmunity; D002291:Carcinoma, Papillary / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D002478:Cells, Cultured; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D050031:Hashimoto Disease / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013961:Thyroid Gland / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013964:Thyroid Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D020381:Interleukin-17; D007371:Interferon-gamma
keywords: Hashimoto thyroiditis; autoimmunity; thyroid cancer; tumor immunity