TNFRSF8 as a Radioligand Therapy Target
TNFRSF8, TNF receptor superfamily member 8, is a cell-surface protein (membrane receptor). In Human Protein Atlas immunohistochemistry, TNFRSF8 staining is highest in head and neck cancer (67% of samples positive), cervical cancer (55% of samples positive) and endometrial cancer (40% of samples positive). Evidence on whether TNFRSF8 internalizes is mixed. Clinical status: Clinical-stage (up to phase 2, any modality).
Is TNFRSF8 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 head and neck cancer, 67% of samples positive.
- ⚠️ Internalization: Mixed evidence.
- ✅ Clinical precedent: Clinical-stage (up to phase 2, any modality)
- ❔ Shedding: Not yet assessed.
- ❔ Normal-tissue dosimetry: Check kidney, liver, bone marrow and salivary expression in the Human Protein Atlas tissue atlas.
TNFRSF8 expression in cancer
Protein expression of TNFRSF8 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 |
|---|---|---|---|
| Head and Neck Cancer | 0.44 | Medium | 67% |
| Cervical Cancer | 0.39 | Medium | 55% |
| Endometrial Cancer | 0.30 | Medium | 40% |
| Bladder Cancer | 0.22 | Medium | 50% |
| Lymphoma | 0.19 | Low | 42% |
| Skin Cancer | 0.19 | Low | 29% |
| Melanoma | 0.17 | Low | 38% |
| Ovarian Cancer | 0.17 | Low | 30% |
| Lung Cancer | 0.17 | Low | 30% |
| Testicular Cancer | 0.14 | Low | 25% |
| Breast Cancer | 0.10 | Low | 20% |
| Thyroid Cancer | 0.08 | Low | 25% |
| Prostate Cancer | 0.03 | Low | 9% |
| Kidney Cancer | 0.03 | Low | 8% |
Not detected by IHC in: colorectal cancer, neuroendocrine tumors, pancreatic cancer, gastric cancer, glioma, liver cancer.
Is TNFRSF8 internalized?
Uncertain. Insufficient literature found.
TNFRSF8 clinical trials
Clinical-stage (up to phase 2, any modality). Nuclens hasn't indexed trials for TNFRSF8 yet. Search ClinicalTrials.gov for TNFRSF8 trials.
TNFRSF8 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 TNFRSF8 in the Human Protein Atlas tissue atlas, and read how normal-tissue expression predicts radioligand dosimetry risk.
TNFRSF8 gene essentiality (DepMap)
CRISPR knockout effect across 1255 cancer cell lines: -0.24 (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 head and neck cancer radioligand targets
EGFR · c-MET (MET) · HER3 (ERBB3) · ITGAV · SSTR2 · B7-H3 (CD276) · STEAP2 · Mesothelin (MSLN)
See all radioligand therapy targets in head and neck 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.