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Related Experiment Video

Updated: Jun 13, 2026

Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate (DMBA-TPA)
04:12

Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate (DMBA-TPA)

Published on: December 19, 2019

Single-Cell Transcriptomic Mapping of PD-L1/TLR4 Remodeling Informs Topical Immunoprevention Timing in Skin

Ran Wei1, Rudramani Pokhrel2, Delaney Stratton2

  • 1Department of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, The University of Arizona, Tucson, Arizona, USA.

Biorxiv : the Preprint Server for Biology
|June 12, 2026
PubMed
Summary

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Early immune signals in sun-damaged skin and actinic keratosis indicate these stages are ideal for topical immunoprevention targeting PD-L1/PD-1 and TLR4 pathways for cutaneous squamous cell carcinoma.

Area of Science:

  • Immunology
  • Dermatology
  • Oncology

Background:

  • Cutaneous squamous cell carcinoma (cSCC) incidence is rising, necessitating effective prevention strategies.
  • Topical immunoprevention targeting PD-L1/PD-1 and TLR4 shows preclinical promise, but optimal timing in humans is unknown.

Purpose of the Study:

  • To define the optimal timing for topical immunoprevention of cSCC by analyzing immune signaling in pre-cancerous lesions.
  • To elucidate the cellular and molecular changes occurring in sun-damaged skin, actinic keratosis, and cSCC.

Main Methods:

  • Single-cell RNA sequencing of matched sun-protected, sun-damaged, and actinic keratosis biopsies, plus cSCC cases.
  • Pseudobulk data analysis to track gene expression changes.
  • Fuzzy c-means trajectory clustering to identify cell-type-specific programs.
Keywords:
PD-L1TLR4actinic keratosiscutaneous squamous cell carcinomasingle-cell RNA sequencing

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Last Updated: Jun 13, 2026

Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate (DMBA-TPA)
04:12

Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate (DMBA-TPA)

Published on: December 19, 2019

Cell Population Analyses During Skin Carcinogenesis
06:53

Cell Population Analyses During Skin Carcinogenesis

Published on: August 21, 2013

Generation of Induced Pluripotent Stem Cells from Human Melanoma Tumor-infiltrating Lymphocytes
10:03

Generation of Induced Pluripotent Stem Cells from Human Melanoma Tumor-infiltrating Lymphocytes

Published on: November 11, 2016

Main Results:

  • Immune checkpoint (PD-L1, CTLA4, PDCD1) and innate inflammatory (TLR4) signals are upregulated in sun-damaged skin, preceding dysplasia.
  • Progressive increases in CD274 (PD-L1), CTLA4, PDCD1, CD27, STAT1, and TLR4-MYD88 signaling were observed from sun-damaged to cSCC stages.
  • Cell-type specific shifts were identified: dendritic cells moved towards PD-L1/IFN-regulatory states, macrophages showed TLR4-associated activation, and T cells indicated a 'hot but exhausted' microenvironment in cSCC.

Conclusions:

  • Sun-damaged skin and actinic keratosis are biologically active stages suitable for early topical immunoprevention.
  • Findings provide a cellular roadmap for developing PD-L1/PD-1 and TLR4 blockade strategies for cSCC prevention.