Targeting CD47 in Anaplastic Thyroid Carcinoma Enhances Tumor Phagocytosis by Macrophages and Is a Promising Therapeutic Strategy.

Schürch, Christian M; Rölli, Matthias A.; Forster, Stefan; Wasmer, Marie-Hélène; Brühl, Frido; Maire, Renaud S.; Di Pancrazio, Sergio; Ruepp, Marc-David; Giger, Roland; Perren, Aurel; Schmitt, Anja M.; Krebs, Philippe; Charles, Roch-Philippe; Dettmer, Matthias S. (2019). Targeting CD47 in Anaplastic Thyroid Carcinoma Enhances Tumor Phagocytosis by Macrophages and Is a Promising Therapeutic Strategy. Thyroid, 29(7), pp. 979-992. Mary Ann Liebert 10.1089/thy.2018.0555

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Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human cancers, with a median survival of only three to six months. Standard treatment options and even targeted therapies have so far failed to improve long-term overall survival. Thus, novel treatment modalities for ATC, such as immunotherapy, are urgently needed. CD47 is a "don't eat me" signal, which prevents cancer cells from phagocytosis by binding to signal regulatory protein alpha on macrophages. So far, the role of macrophages and the CD47-signal regulatory protein alpha signaling axis in ATC is not well understood.
This study analyzed 19 primary human ATCs for macrophage markers, CD47 expression, and immune checkpoints by immunohistochemistry. ATC cell lines and a fresh ATC sample were assessed by flow cytometry for CD47 expression and macrophage infiltration, respectively. CD47 was blocked in phagocytosis assays of co-cultured macrophages and ATC cell lines. Anti-CD47 antibody treatment was administered to ATC cell line xenotransplanted immunocompromised mice, as well as to tamoxifen-induced ATC double-transgenic mice.
Human ATC samples were heavily infiltrated by CD68- and CD163-expressing tumor-associated macrophages (TAMs), and expressed CD47 and calreticulin, the dominant pro-phagocytic molecule. In addition, ATC tissues expressed the immune checkpoint molecules programmed cell death 1 and programmed death ligand 1. Blocking CD47 promoted the phagocytosis of ATC cell lines by macrophages in vitro. Anti-CD47 antibody treatment of ATC xenotransplanted mice increased the frequency of TAMs, enhanced the expression of macrophage activation markers, augmented tumor cell phagocytosis, and suppressed tumor growth. In double-transgenic ATC mice, CD47 was expressed on tumor cells, and blocking CD47 increased TAM frequencies.
Targeting CD47 or CD47 in combination with programmed cell death 1 may potentially improve the outcomes of ATC patients and may represent a valuable addition to the current standard of care.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Ear, Nose and Throat Disorders (ENT)
04 Faculty of Medicine > Service Sector > Institute of Pathology > Molecular Pathology
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine
04 Faculty of Medicine > Service Sector > Institute of Pathology
08 Faculty of Science > Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP)
04 Faculty of Medicine > Service Sector > Institute of Pathology > Immunopathology

UniBE Contributor:

Rölli, Matthias Andreas, Forster, Stefan, Wasmer, Marie-Hélène Christin, Brühl, Frido, Maire, Renaud Sylvain, Ruepp, Marc-David, Giger, Roland, Perren, Aurel, Schmitt Kurrer, Anja, Krebs, Philippe, Charles, Roch-Philippe, Dettmer, Matthias


500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health
500 Science > 540 Chemistry




Mary Ann Liebert




Matthias Dettmer

Date Deposited:

25 Sep 2019 10:44

Last Modified:

05 Dec 2022 15:30

Publisher DOI:


PubMed ID:


Uncontrolled Keywords:

CD47 anaplastic thyroid carcinoma immune checkpoints phagocytosis programmed cell death 1 tumor-associated macrophages




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