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Major Histocompatibility Complex Genes as Therapeutic Opportunity for Immune Cold Molecular Cancer Subtypes

Paweł Karpiński1,2, Łukasz Łaczmański2, Maria M Sąsiadek1

  • 1Department of Genetics, Wroclaw Medical University, Wroclaw, Poland.

Journal of Immunology Research
|December 7, 2020
PubMed

Insights

Many cancer immunotherapies fail due to poor major histocompatibility complex (MHC) gene expression. This study found MHC-low expression in over half of molecular cancer subtypes, highlighting a need to boost MHC levels for better treatment response.

Area of Science:

  • Oncology
  • Immunology
  • Genomics

Background:

  • Current immunotherapies benefit only a subset of patients.
  • Tumor antigen presentation defects and molecular heterogeneity limit treatment efficacy.
  • Major histocompatibility complex (MHC) gene expression deregulation across cancer subtypes remains poorly understood.

Purpose of the Study:

  • To characterize major histocompatibility complex (MHC) gene expression patterns within distinct molecular cancer subtypes.
  • To identify cancer subtypes with significantly decreased MHC gene expression.
  • To inform strategies for improving immunotherapy effectiveness.

Main Methods:

  • Analyzed 13 The Cancer Genome Atlas (TCGA) cancer types (5651 tumors, 485 normal tissues).
  • Removed genes correlated with immune infiltrates to isolate tumor-specific expression.
  • Performed unsupervised clustering on 14 MHC genes to identify expression patterns.
  • Compared MHC clusters based on other immune-related gene expression.

Main Results:

  • Discovered three distinct major histocompatibility complex (MHC) expression clusters.
  • Identified concordantly decreased MHC gene expression (MHC-low) in 26 of 55 molecular subtypes.
  • MHC-low subtypes represent a significant portion of cancers studied.

Conclusions:

  • A substantial number of molecular cancer subtypes exhibit significantly reduced MHC gene expression.
  • Strategies to enhance tumor MHC expression are crucial for improving immunotherapy outcomes.
  • Boosting MHC expression may enhance rejection of "immune cold" tumors by cytotoxic T lymphocytes.

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