Galectin-3 and TREM2: a myeloid axis as a predictive biomarker for immune checkpoint inhibitors in cancer
4 affiliations
- 1Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University
- 2The Second Clinical Medical College of Shaanxi University of Chinese Medicine
- 3Department of Ophthalmology, Tangdu Hospital, Air Force Medical University
- 4Department of Cardiothoracic Surgery, The 920th Hospital of Joint Logistics Support Force
Abstract
The ligand-receptor relationship between Galectin-3 and TREM2 has been identified in lung cancer. High expression of both is associated with anti-PD-1 efficacy, suggesting that the combination of both may predict the benefit of immune checkpoint inhibitors (ICIs). This review comprises five sections presenting the structure/expression, interaction, immunomodulatory roles, spatial profiling, and clinical application of Galectin-3/TREM2. The carbohydrate-recognition domain (CRD) of Galectin-3 and the immunoglobulin (Ig) domain of TREM2 are the Galectin-3-TREM2 interaction domains. Galectin-3 is mainly secreted by tumor cells, stromal cells and tumor-associated macrophages (TAMs), while TREM2 is expressed on myeloid cells, especially macrophages. Galectin-3 and TREM2 reduce T cell and NK cell function, promote M2 polarization of macrophages, and remodel the myeloid microenvironment. Both Galectin-3 and TREM2 show potential in predicting ICI benefit in lung cancer, but prediction studies combining Galectin-3 and TREM2 have not yet been reported. Preclinical evidence supports that Galectin-3/TREM2 dual inhibition can suppress tumor progression in lung cancer models. In clinical studies, Galectin-3 inhibitors Belapectin and GB1211 show acceptable safety, and Belapectin plus pembrolizumab shows certain efficacy in solid tumors. However, the TREM2 inhibitor PY314 showed limited efficacy in renal cell carcinoma, suggesting the need for improved antibody design and better patient selection. We present a comprehensive overview of the role of Galectin-3/TREM2 in cancer, suggesting novel strategies for predicting ICI benefit.
Related
- Tissue galectin-3 as a potential prognostic biomarker in type 2 diabetes patients with hepatocellular carcinoma: in vitro and in silico approaches
- Commentary: Hemophagocytic lymphohistiocytosis induced by immune checkpoint inhibitors: observations and proposed clinical management
- Immune checkpoint inhibitors and the inflammatory dysregulation: decoding cutaneous and gastrointestinal immune-related adverse events for the allergist and immunologist
- 454 Second primary hematologic malignancies in melanoma survivors before and after the introduction of immune checkpoint inhibitors: a population-based SEER analysis
- VISTA as an emerging immune checkpoint in cervical cancer: spatial immune regulation, myeloid–T Cell crosstalk, and therapeutic opportunities
BibTeX
@article{zhang2026galectin3,
title = {{Galectin-3 and TREM2: a myeloid axis as a predictive biomarker for immune checkpoint inhibitors in cancer}},
author = {Runze Zhang and Junyang Pan and Nan Ma and Xiyang Tang and Jinbo Zhao},
journal = {Frontiers in Immunology},
year = {2026},
month = nov,
doi = {10.3389/fimmu.2026.2008356},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.2008356/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Galectin-3 and TREM2: a myeloid axis as a predictive biomarker for immune checkpoint inhibitors in cancer
AU - Runze Zhang
AU - Junyang Pan
AU - Nan Ma
AU - Xiyang Tang
AU - Jinbo Zhao
PY - 2026
DA - 2026/11/03
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.2008356
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.2008356/full
AB - The ligand-receptor relationship between Galectin-3 and TREM2 has been identified in lung cancer. High expression of both is associated with anti-PD-1 efficacy, suggesting that the combination of both may predict the benefit of immune checkpoint inhibitors (ICIs). This review comprises five sections presenting the structure/expression, interaction, immunomodulatory roles, spatial profiling, and clinical application of Galectin-3/TREM2. The carbohydrate-recognition domain (CRD) of Galectin-3 and the immunoglobulin (Ig) domain of TREM2 are the Galectin-3-TREM2 interaction domains. Galectin-3 is mainly secreted by tumor cells, stromal cells and tumor-associated macrophages (TAMs), while TREM2 is expressed on myeloid cells, especially macrophages. Galectin-3 and TREM2 reduce T cell and NK cell function, promote M2 polarization of macrophages, and remodel the myeloid microenvironment. Both Galectin-3 and TREM2 show potential in predicting ICI benefit in lung cancer, but prediction studies combining Galectin-3 and TREM2 have not yet been reported. Preclinical evidence supports that Galectin-3/TREM2 dual inhibition can suppress tumor progression in lung cancer models. In clinical studies, Galectin-3 inhibitors Belapectin and GB1211 show acceptable safety, and Belapectin plus pembrolizumab shows certain efficacy in solid tumors. However, the TREM2 inhibitor PY314 showed limited efficacy in renal cell carcinoma, suggesting the need for improved antibody design and better patient selection. We present a comprehensive overview of the role of Galectin-3/TREM2 in cancer, suggesting novel strategies for predicting ICI benefit.
SN - 1664-3224
ER -