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Updated: May 22, 2026

In Vitro Resident Memory CD8 T Cell Differentiation Using Epithelial Organoid-T Cell Co-culture System
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In Vitro Resident Memory CD8 T Cell Differentiation Using Epithelial Organoid-T Cell Co-culture System

Published on: February 3, 2026

Protocadherin-18 is a novel differentiation marker and an inhibitory signaling receptor for CD8+ effector memory T

Edwin J Vazquez-Cintron1, Ngozi R Monu, Jeremy C Burns

  • 1Department of Cell Biology, New York University Langone School of Medicine New York, New York, United States of America.

Plos One
|May 9, 2012
PubMed

Insights

A novel protein, Protocadherin-18 (pcdh18), was identified in CD8(+) tumor-infiltrating T cells (TIL). Pcdh18 restricts T cell effector functions by inhibiting T cell receptor signaling.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • CD8(+) T cells infiltrating tumors (TIL) often exhibit impaired effector functions.
  • This dysfunction is linked to defective T cell receptor (TCR)-mediated signaling, associated with p56(lck) kinase inactivation.

Purpose of the Study:

  • To identify novel molecules involved in the regulation of CD8(+) TIL effector functions.
  • To characterize the role of Protocadherin-18 (pcdh18) in T cell signaling and function.

Main Methods:

  • Identification of pcdh18 as a p56(lck) interacting partner in nonlytic TIL.
  • Analysis of pcdh18 transcription during CD8(+) T cell activation and memory conversion.
  • Experimental induction of pcdh18 expression in primary CD8(+) effector cells.

Main Results:

  • Pcdh18 is transcribed during the transition of CD8(+) central memory T cells to effector memory cells.
  • Expression of pcdh18 in CD8(+) effector cells recapitulates the nonlytic TIL phenotype, including defective TCR signaling, reduced cytokine secretion, and impaired cytolysis.
  • Pcdh18 contains a conserved motif crucial for its inhibitory function.

Conclusions:

  • Pcdh18 is a novel activation marker for CD8(+) memory T cells.
  • Pcdh18 acts as an inhibitory signaling receptor, restricting the effector phase of CD8(+) T cell responses.
  • Pcdh18 represents a potential therapeutic target for enhancing anti-tumor immunity.

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