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Isolation and Expansion of Cytotoxic Cytokine-induced Killer T Cells for Cancer Treatment
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Cytotoxic lymphocytes target characteristic biophysical vulnerabilities in cancer

Maria Tello-Lafoz1, Katja Srpan2, Elisa E Sanchez3

  • 1Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Immunity
|March 23, 2021
PubMed

Insights

Myocardin-related transcription factors (MRTFs) sensitize cancer cells to immune attack. Overexpressing MRTFs enhances cancer cell elimination by immune cells and improves responses to immune checkpoint blockade therapy.

Area of Science:

  • Immunology
  • Cancer Biology
  • Biophysics

Background:

  • Immune cells eliminate tumors via recognition of oncogenic transformation markers.
  • Myocardin-related transcription factors (MRTFs) are known to promote cancer cell migration and invasion.

Purpose of the Study:

  • To investigate the role of MRTFs in cancer cell sensitization to the immune system.
  • To explore the potential of MRTF signaling as a therapeutic target for enhancing anti-cancer immunity.

Main Methods:

  • Utilized mouse models of melanoma and breast cancer metastasis.
  • Employed cytotoxic lymphocyte assays and immune checkpoint blockade (ICB) antibody treatments.
  • Conducted biophysical and functional assays to assess cytoskeletal mechanics and immune cell interactions.

Main Results:

  • High MRTF expression in cancer cells led to selective elimination by cytotoxic lymphocytes.
  • Immune checkpoint blockade further enhanced this immunosurveillance phenotype.
  • MRTF overexpression increased cancer cell cytoskeletal rigidity, increasing vulnerability to T cells and NK cells.
  • High MRTF signaling correlated with ICB efficacy in human melanoma patients.

Conclusions:

  • MRTFs sensitize cancer cells to immune surveillance, offering a novel therapeutic avenue.
  • Mechanosurveillance, a mechanical dimension of immunosurveillance, is critical for targeting metastatic cancer.
  • Targeting MRTF signaling may enhance the efficacy of immunotherapies like ICB.
Keywords:
NK cellT cellcancer immunologycheckpoint blockade therapycytotoxicityimmunosurveillancemechanobiologymetastasismyocardin related transcription factor

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