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Updated: May 28, 2025

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MAP1LC3C repression reduces CIITA- and HLA class II expression in non-small cell lung cancer

Lydie M O Barbeau1, Nicky A Beelen2,3, Kim G Savelkouls1

  • 1Department of Radiation Oncology (Maastro), GROW - School for Oncology and Reproduction, Maastricht University Medical Center+, Maastricht, The Netherlands.

Plos One
|February 10, 2025
PubMed

Insights

Lung squamous cell carcinoma (LUSC) evades immune attack by reducing MAP1LC3C expression. Low MAP1LC3C hinders immune cell recognition, impacting immunotherapy effectiveness.

Area of Science:

  • Oncology
  • Immunology
  • Genetics

Background:

  • Lung squamous cell carcinoma (LUSC) treatment has advanced with immune checkpoint inhibitors (ICI), benefiting about 25% of patients.
  • Challenges persist, including identifying predictive biomarkers and understanding immune resistance mechanisms in LUSC.
  • Tumor cells can become "immune-cold," evading immune detection and response.

Purpose of the Study:

  • To investigate the role of Microtubule-Associated Protein 1 Light Chain 3 Gamma (MAP1LC3C) in LUSC immune evasion.
  • To explore the relationship between MAP1LC3C expression and immune cell infiltration and antigen presentation machinery.

Main Methods:

  • Analysis of The Cancer Genome Atlas (TCGA) datasets for LUSC.
  • Correlation analysis between MAP1LC3C expression and immune markers (CIITA, HLA).
  • Experimental manipulation of MAP1LC3C expression in tumor cells to assess downstream effects.

Main Results:

  • Reduced MAP1LC3C expression was observed in LUSC tumors.
  • Low MAP1LC3C correlated with decreased CIITA and HLA class II expression.
  • Silencing MAP1LC3C in tumor cells led to reduced CIITA and HLA class II production, and decreased immune cell infiltration.

Conclusions:

  • LUSC cells may downregulate MAP1LC3C to evade immune surveillance.
  • Low MAP1LC3C expression is linked to reduced antigen presentation and immune cell infiltration.
  • Targeting MAP1LC3C could potentially enhance anti-tumor immunity in LUSC.

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