TAP1

Overview

TAP1 (Transporter Associated with Antigen Processing 1) is a component of the MHC class I antigen presentation pathway, encoded in the MHC locus. TAP1 forms a heterodimer with TAP2 to transport peptides into the endoplasmic reticulum for loading onto MHC class I molecules. In the context of high-grade serous ovarian carcinoma (HGSOC) and its fallopian tube precursors (STICs and p53 signatures), TAP1 is an interferon-stimulated gene (ISG) upregulated as early as the p53 signature stage, reflecting constitutive chromosomal-instability-driven IFN signaling.

Alterations observed in the corpus

  • TAP1 is one of the IFN-stimulated genes (ISGs) significantly upregulated from the p53 signature (p53.I) stage onward across the HGSOC progression axis (p53.I → STIC.I → STIC.C → cancer) in a 44-specimen FFPE fallopian tube study profiled by CyCIF and GeoMx WTA spatial transcriptomics PMID:39386723.
  • Bayesian ordinal regression confirms TAP1 upregulation at every stage above matched normal fallopian tube (FT) epithelium, alongside STAT1, IFITM1, IRF7, IRF9, ISG15, and MX1 PMID:39386723.
  • TAP1 expression is part of a coordinated HLA-E-positive antigen-presentation program in STIC.I epithelium (co-expressed with HLA-A, HLA-B, HLA-DRA, TAPBP, complement genes, MYC, and multiple ISGs) PMID:39386723.
  • Component of the MHC class I antigen-processing machinery (APM); enriched for somatic mutations in TIL-rich colorectal tumors, consistent with immune-escape selection pressure, in a cohort of 619 CRC cases PMID:27149842.

Cancer types (linked)

  • HGSOC — TAP1 is constitutively upregulated in HGSOC precursors (p53.I, STIC.I) and maintained through STIC.C and invasive cancer; the IFN-pathway activation is independent of BRCA1/BRCA2 germline status PMID:39386723.

Co-occurrence and mutual exclusivity

Therapeutic relevance

  • The antigen-presentation program including TAP1 was observed to be paradoxically insufficient to prevent immune escape; instead, HLA-E upregulation engages NKG2A on NK cells to suppress NK cytotoxicity. Anti-NKG2A monotherapy (e.g., monalizumab) is proposed to re-arm NK cells against TAP1/HLA-E-high STIC lesions — a hypothesis not yet tested in intervention studies PMID:39386723.

Open questions

  • Whether TAP1 upregulation is caused by cGAS-STING signaling from micronuclear rupture or by alternative upstream IFN inducers in fallopian tube precursors has not been directly established PMID:39386723.
  • Whether TAP1-high STIC lesions have higher malignant transformation potential than TAP1-low lesions is not tested PMID:39386723.

Sources

This page was processed by crosslinker on 2026-05-04. - PMID:27149842

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