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Flow Cytometry-Based Isolation and Therapeutic Evaluation of Tumor-Infiltrating Lymphocytes in a Mouse Model of Pancreatic Cancer
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The CD155/TIGIT axis promotes and maintains immune evasion in neoantigen-expressing pancreatic cancer

William A Freed-Pastor1, Laurens J Lambert2, Zackery A Ely2

  • 1David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

Cancer Cell
|August 6, 2021
PubMed

Insights

Pancreatic cancer evades immune attack by exploiting the CD155/TIGIT pathway. Targeting this axis with combination immunotherapy shows promise for treating pancreatic adenocarcinoma (PDAC).

Area of Science:

  • Immunology
  • Oncology
  • Virology

Background:

  • Pancreatic adenocarcinoma (PDAC) is a lethal cancer with limited treatment options.
  • Immune evasion is a key mechanism hindering effective cancer therapies.
  • The CD155/TIGIT axis plays a role in immune suppression during chronic infections and cancer.

Purpose of the Study:

  • To investigate the role of the CD155/TIGIT axis in immune evasion in PDAC.
  • To identify potential therapeutic strategies targeting this axis for PDAC treatment.

Main Methods:

  • Analysis of PDAC for neoantigens.
  • Preclinical models of neoantigen-expressing PDAC.
  • Genetic and pharmacologic modulation of the CD155/TIGIT axis.
  • Evaluation of combination immunotherapy (TIGIT/PD-1 co-blockade plus CD40 agonism).

Main Results:

  • PDAC harbors predicted high-affinity neoantigens, even in advanced disease.
  • Neoantigen-specific CD8+ T cells in PDAC exhibit dysfunction.
  • Modulation of the CD155/TIGIT axis impacts immune evasion in PDAC models.
  • A combination immunotherapy demonstrated significant anti-tumor responses in preclinical models.

Conclusions:

  • The CD155/TIGIT axis is crucial for immune evasion in PDAC.
  • Combination immunotherapy targeting TIGIT/PD-1 and CD40 agonism is a promising strategy for PDAC treatment.
  • This approach warrants clinical evaluation for patients with pancreatic cancer.
Keywords:
CD155TIGITimmune evasionimmunotherapypancreatic cancer

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