PTPN22 as a Radioligand Therapy Target
PTPN22, protein tyrosine phosphatase non-receptor type 22, is a cell-surface protein (membrane receptor). In Human Protein Atlas immunohistochemistry, PTPN22 staining is highest in colorectal cancer (100% of samples positive), kidney cancer (100% of samples positive) and thyroid cancer (100% of samples positive). Published literature reports that PTPN22 internalizes after ligand binding, which helps retain a radionuclide inside tumor cells. Clinical status: Discovery-stage (no clinical drug program).
Is PTPN22 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: High IHC staining in colorectal cancer, 100% of samples positive.
- ✅ Internalization: Reported to internalize, which favors radionuclide retention.
- ⚠️ 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.
PTPN22 expression in cancer
Protein expression of PTPN22 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 |
|---|---|---|---|
| Colorectal Cancer | 0.83 | High | 100% |
| Kidney Cancer | 0.76 | High | 100% |
| Thyroid Cancer | 0.75 | High | 100% |
| Breast Cancer | 0.72 | High | 100% |
| Head and Neck Cancer | 0.67 | High | 100% |
| Endometrial Cancer | 0.67 | High | 100% |
| Liver Cancer | 0.67 | High | 100% |
| Ovarian Cancer | 0.64 | High | 100% |
| Lymphoma | 0.64 | High | 100% |
| Skin Cancer | 0.61 | High | 92% |
| Prostate Cancer | 0.56 | High | 100% |
| Glioma | 0.56 | High | 100% |
| Testicular Cancer | 0.53 | High | 100% |
| Gastric Cancer | 0.52 | High | 89% |
| Melanoma | 0.50 | Medium | 100% |
| Pancreatic Cancer | 0.50 | Medium | 83% |
| Lung Cancer | 0.42 | Medium | 91% |
| Neuroendocrine Tumors | 0.42 | Medium | 100% |
| Cervical Cancer | 0.42 | Medium | 75% |
| Bladder Cancer | 0.30 | Medium | 82% |
Is PTPN22 internalized?
Yes. PTPN22 regulates TCR internalization and recycling via the modulation of the TCR signaling pathway.
Sources: PMID 37833951 · PMID 29040339 · PMID 28437437. AI-extracted from abstracts, so verify before citing.
PTPN22 clinical trials
Discovery-stage (no clinical drug program). Nuclens hasn't indexed trials for PTPN22 yet. Search ClinicalTrials.gov for PTPN22 trials.
PTPN22 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 PTPN22 in the Human Protein Atlas tissue atlas, and read how normal-tissue expression predicts radioligand dosimetry risk.
PTPN22 gene essentiality (DepMap)
CRISPR knockout effect across 1257 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 colorectal cancer radioligand targets
c-MET (MET) · HER3 (ERBB3) · FAP · EGFR · CEA (CEACAM5) · EPCAM · SSTR2 · STEAP2
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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.