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Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells
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Regulation of the antigen presentation machinery in cancer and its implication for immune surveillance

Adithya Balasubramanian1,2,3, Thomas John3, Marie-Liesse Asselin-Labat1,2

  • 1Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.

Biochemical Society Transactions
|March 28, 2022
PubMed

Insights

Cancer cells evade immune attack by reducing antigen presentation machinery, specifically MHC-I and MHC-II. Reactivating these molecules may enhance anti-tumour immunity and improve patient survival outcomes in cancer immunotherapy.

Area of Science:

  • Immunology
  • Oncology
  • Molecular Biology

Background:

  • Cancer cells employ immune evasion strategies, including down-regulating antigen presentation machinery like MHC-I and MHC-II, to escape immune destruction.
  • Reduced expression of Major Histocompatibility Complex (MHC) class I and class II proteins impairs the presentation of tumor neoantigens to CD8+ and CD4+ T lymphocytes, respectively.
  • While MHC-I evasion is studied, the role of MHC-II on tumor cells and its potential for harnessing anti-tumor immunity is an emerging area of interest.

Purpose of the Study:

  • To provide a comprehensive overview of mechanisms used by tumor cells to reduce MHC-I and MHC-II expression.
  • To outline current strategies for reversing these immunosuppressive processes.
  • To highlight the potential of MHC-I and MHC-II reactivation for improving cancer immunotherapy response and patient survival.

Main Methods:

  • Literature review of conserved and novel mechanisms of MHC-I and MHC-II downregulation in cancer.
  • Analysis of preclinical and clinical approaches aimed at restoring MHC expression on tumor cells.
  • Synthesis of findings related to the impact of MHC expression on anti-tumor immunity and patient outcomes.

Main Results:

  • Tumor cells utilize diverse mechanisms to downregulate MHC-I and MHC-II expression, thereby evading T cell recognition and promoting immune escape.
  • Reactivation of tumor-specific MHC-I and MHC-II expression is associated with improved patient survival in various clinical studies.
  • Targeting MHC expression presents a promising strategy to enhance the efficacy of cancer immunotherapies.

Conclusions:

  • Understanding and reversing tumor-induced downregulation of MHC-I and MHC-II is crucial for developing effective cancer immunotherapies.
  • Restoring antigen presentation through MHC reactivation holds significant potential for improving anti-tumor immune responses and patient survival.
  • Further research and clinical trials are warranted to translate these findings into improved cancer treatment strategies.
Keywords:
cancerimmune responsemajor histocompatibility complex

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