Profiling Dectin-2-Positive Tumor-Associated Macrophages Across Human Cancers by Immunohistochemistry

Area of Science:

• Immunology
• Oncology
• Cancer Biology

Background:

• Dectin-2 is a C-type lectin receptor expressed on myeloid cells.
• Tumor-associated macrophages (TAMs) play complex roles in cancer progression and immune response.
• Understanding Dectin-2 expression in TAMs is crucial for developing targeted cancer immunotherapies.

Purpose of the Study:

• To determine the prevalence and distribution of Dectin-2-positive macrophages in various human tumors.
• To develop and validate a research immunohistochemistry (IHC) assay for Dectin-2 detection in cancer tissues.

Main Methods:

• Gene expression analysis of CLEC6A (encoding Dectin-2) across 38 tumor types using The Cancer Genome Atlas (TCGA).
• Development and validation of a Dectin-2 IHC assay using a selected monoclonal antibody.
• Assessment of Dectin-2 expression in tissue microarrays (TMAs) and whole tissue sections (WTSs) across multiple cancer types.

Main Results:

• TCGA analysis revealed enriched CLEC6A expression in non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), head and neck cancer (HNC), and colorectal cancer (CRC).
• IHC confirmed Dectin-2-positive macrophages in various tumors, with notable heterogeneity.
• NSCLC, melanoma, HNC, TNBC, and CRC showed higher frequencies of Dectin-2-positive macrophage infiltration in WTS analysis.

Conclusions:

• Dectin-2 is expressed on a subset of TAMs across multiple human cancers, particularly enriched in NSCLC, melanoma, HNC, TNBC, and CRC.
• This study provides the first broad protein-level characterization of Dectin-2 in human tumors.
• The developed IHC assay and findings lay the groundwork for future translational studies investigating Dectin-2-targeted cancer therapies.