Increased cytoplasmatic expression of cancer immune surveillance receptor CD1d in anaplastic thyroid carcinomas

Cancer Med. 2019 Nov;8(16):7065-7073. doi: 10.1002/cam4.2573. Epub 2019 Sep 27.

Abstract

Background: Anaplastic thyroid carcinomas are associated with rapid tumor growth, short survival time and without any promising therapy to improve the poor prognosis. In this study, expression of immunoregulative receptor CD1d and lymphocyte infiltration in different thyroid tumors as well as in healthy tissue were analyzed in order to find new targets for an immunotherapeutic approach.

Methods: CD1d immunohistochemistry was performed in samples of 18 anaplastic, 17 follicular, 27 papillary, and 4 medullary thyroid carcinomas as well as in 19 specimens from normal thyroid tissue and additionally in 10 samples of sarcoma, seven malignant melanoma and three spindle-cell lung carcinoma. Furthermore, thyroid samples were stained with antibodies against CD3, CD20, CD56, CD68, and LCA in order to analyze lymphocyte infiltration.

Results: For the first time CD1d receptor expression on normal thyroid tissue could be demonstrated. Moreover, anaplastic thyroid carcinomas showed significantly higher expression levels compared to other thyroid samples. Most astonishingly, CD1d expression disappeared from the cellular surface and was detected rather in the cytoplasm of anaplastic thyroid carcinoma cells. In addition, histologically similar tumors to anaplastic carcinoma like sarcoma and malignant melanoma revealed distinct CD1d staining patterns. Furthermore, infiltration of T cells, B cells, and macrophages in anaplastic thyroid carcinomas was different when compared to normal thyroid tissue and all other thyroid carcinomas.

Conclusions: Anaplastic thyroid carcinomas show significantly higher expression of CD1d, a receptor for NKT cells, which are subject of several anticancer therapy studies. These results may offer a novel approach to explore immunotherapeutic treatment options.

Keywords: CD1d; NKT cell; immunotherapy; lymphocyte infiltration; thyroid carcinoma.

MeSH terms

  • Antigens, CD1d / immunology*
  • B-Lymphocytes / immunology
  • Carcinoma, Neuroendocrine / immunology
  • Carcinoma, Papillary / immunology
  • Cytoplasm / immunology*
  • Humans
  • Macrophages / immunology
  • T-Lymphocytes / immunology
  • Thyroid Carcinoma, Anaplastic / immunology*
  • Thyroid Gland / immunology
  • Thyroid Neoplasms / immunology

Substances

  • Antigens, CD1d
  • CD1D protein, human

Supplementary concepts

  • Thyroid cancer, medullary