Galectin-3: an immune checkpoint target for musculoskeletal tumor patients
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CLINICAL
Galectin-3: an immune checkpoint target for musculoskeletal tumor patients Kosei Nakajima 1,2
&
Vitaly Balan 3 & Avraham Raz 4
Received: 6 August 2020 / Accepted: 4 September 2020 # The Author(s) 2020
Abstract In the past decade, the development of immune checkpoint inhibitors in oncological clinical settings was in the forefront. However, the interest in musculoskeletal tumor patients as candidates for checkpoint inhibition remains underserved. Here, we are forwarding evidence proposing that galectin-3 (Gal-3) is an additional immune factor in the checkpoint processes. This review is the result of a large-scale cohort study depicting that overexpression of Gal-3 was widely prevalent in patients with musculoskeletal tumors, whereas T cell infiltrations were generally suppressed in the tumor microenvironment. Targeting Gal-3 would serve as a novel immune checkpoint inhibitor candidate in patients afflicted with aggressive musculoskeletal tumors. Keywords Musculoskeletal tumors . Galectin-3 . Immune checkpoint inhibitor . Bone immunological microenvironment
1 Galectin-3 discovery In the early 1980s, limited biochemical differences among tumor cells with low or high metastatic potentials were reported, and the specific surface characteristics associated with metastasis were still undefined. It was shown that tumor cell aggregation and pulmonary metastasis can correlate with distribution of cell surface dense anionic sites [1]. The following year, in 1981, a simple sugar, galactose was reported to inhibit the formation of tumor emboli, leading to the notion that tumor cells express galactose-binding proteins, i.e., lectin. The carbohydrate-binding protein(s) on the surface of malignant
* Kosei Nakajima [email protected]
cells had been implicated in tumor aggressive behaviors. At that time, it was termed ‘galactoside-specific lectin’ [2]. In 1994, the protein was firstly named ‘galectin-3’ (Gal-3) [3]. Since then, identification studies have clarified that the molecule was also known as IgE-binding protein, MAC2, L-29, CPB-35, etc., since the names had not been organized at that time. Additionally, 14 other galectins were discovered and the family has been classified into three groups according to their structure: (1) prototypical, (2) tandem repeat, and (3) chimeric. In human cells, Gal-1-Gal-15 all express an evolutionarily conserved carbohydrate recognition domain (CRD) that interacts with various glycoproteins containing terminal galactoside residues [4]. One of them, e.g., Gal-3, was found to be a pleiotropic-pluripotent molecule. Presently, consensus is that Gal-3 works as a key driver of tumor progression and is considered a promising therapeutic target.
* Avraham Raz [email protected] 1
Division of Translational Research, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-Ku, Tokyo 104-0045, Japan
2
Division of Veterinary Oncology and Surgery, Faculty of Veterinary Medicine, Imabari Campus, Okayama University of Science, 1-3
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