TREM2 as a Radioligand Therapy Target
TREM2, triggering receptor expressed on myeloid cells 2, is a cell-surface protein (membrane receptor). In Human Protein Atlas immunohistochemistry, TREM2 staining is highest in pancreatic cancer (100% of samples positive), ovarian cancer (67% of samples positive) and thyroid cancer (75% of samples positive). Evidence on whether TREM2 internalizes is mixed. Clinical status: Discovery-stage (no clinical drug program).
Is TREM2 a good radioligand therapy target?
Scored against the six criteria that decide whether a protein can become a radioligand therapy:
- ✅ Cell-surface accessibility: Localized to the cell surface, so a radioligand can reach it from circulation.
- ⚠️ Tumor expression: Medium IHC staining in pancreatic cancer, 100% of samples positive.
- ⚠️ Internalization: Mixed evidence.
- ⚠️ Clinical precedent: Discovery-stage (no clinical drug program)
- ❔ Shedding: Not yet assessed.
- ❔ Normal-tissue dosimetry: Check kidney, liver, bone marrow and salivary expression in the Human Protein Atlas tissue atlas.
TREM2 expression in cancer
Protein expression of TREM2 across 20 cancer types from Human Protein Atlas immunohistochemistry. The score is a weighted staining intensity from 0 to 1; "% positive" is the share of patient samples with detectable staining.
| Cancer type | IHC score | Level | % positive |
|---|---|---|---|
| Pancreatic Cancer | 0.50 | Medium | 100% |
| Ovarian Cancer | 0.44 | Medium | 67% |
| Thyroid Cancer | 0.42 | Medium | 75% |
| Liver Cancer | 0.37 | Medium | 78% |
| Breast Cancer | 0.36 | Medium | 50% |
| Gastric Cancer | 0.33 | Medium | 75% |
| Melanoma | 0.33 | Medium | 73% |
| Lung Cancer | 0.31 | Medium | 58% |
| Colorectal Cancer | 0.28 | Medium | 58% |
| Cervical Cancer | 0.25 | Medium | 58% |
| Head and Neck Cancer | 0.25 | Medium | 50% |
| Endometrial Cancer | 0.18 | Low | 36% |
| Bladder Cancer | 0.17 | Low | 42% |
| Kidney Cancer | 0.12 | Low | 36% |
| Prostate Cancer | 0.11 | Low | 33% |
| Glioma | 0.06 | Low | 8% |
Not detected by IHC in: skin cancer, lymphoma, neuroendocrine tumors, testicular cancer.
Is TREM2 internalized?
Uncertain. The abstracts do not specifically mention whether TREM2 undergoes internalization or endocytosis upon ligand or antibody binding. They focus more on the functions and interactions of APOE and its receptors, including TREM2, without detailing specific processes like internalization.
Sources: PMID 42362005 · PMID 41945876 · PMID 41929946 · PMID 41648425 · PMID 41487996. AI-extracted from abstracts, so verify before citing.
TREM2 clinical trials
Discovery-stage (no clinical drug program). Nuclens hasn't indexed trials for TREM2 yet. Search ClinicalTrials.gov for TREM2 trials.
TREM2 normal tissue expression
Normal-tissue expression in dose-limiting organs (kidney, liver, bone marrow, salivary glands) drives radioligand dosimetry risk. Nuclens is re-validating its normal-tissue values, so they are not shown here yet. See TREM2 in the Human Protein Atlas tissue atlas, and read how normal-tissue expression predicts radioligand dosimetry risk.
TREM2 gene essentiality (DepMap)
CRISPR knockout effect across 1230 cancer cell lines: 0.02 (not essential). Radioligands kill by radiation, not by blocking the target, so essentiality matters less than for inhibitors. A non-essential target can still be an excellent radioligand target.
Related pancreatic cancer radioligand targets
EGFR · HER3 (ERBB3) · c-MET (MET) · Mesothelin (MSLN) · FAP · CEA (CEACAM5) · STEAP2 · SSTR2
See all radioligand therapy targets in pancreatic cancer.
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Subcellular localization: UniProt via Open Targets (CC BY 4.0 / CC0). Tumor immunohistochemistry: Human Protein Atlas (CC BY-SA 4.0). Clinical trials: ClinicalTrials.gov (public domain). Gene essentiality: DepMap (CC BY 4.0). Internalization and shedding: AI-extracted from PubMed abstracts, so verify against the cited papers before relying on them. Nuclens is a first-pass triage layer, not a substitute for wet-lab validation or clinical dosimetry. Derived expression data on this page is shared under CC BY-SA 4.0.