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Studying the Immunomodulatory Functions of PARP1 and PARP2 in Mouse Models of Cancer

Nura Lutfi1, Carlos Martínez2, José Yélamos3,4

  • 1Cancer Research Program, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.

Methods in Molecular Biology (Clifton, N.J.)
|December 14, 2022
PubMed

Insights

Poly(ADP-ribose) polymerases (PARP1 and PARP2) are crucial in DNA damage response and cancer therapy. New evidence shows PARP1 and PARP2 also modulate anti-tumor immunity, impacting cancer progression.

Area of Science:

  • Biochemistry
  • Immunology
  • Oncology

Background:

  • Poly-ADP-ribosylation, mediated by PARP1 and PARP2, is central to the DNA damage response (DDR).
  • PARP inhibitors (PARPi) are established cancer therapeutics targeting DDR, primarily for their direct effects on tumor cells.
  • Emerging evidence highlights the immunomodulatory roles of PARP1 and PARP2, influencing the anti-tumor immune response and potentially affecting tumor progression.

Purpose of the Study:

  • To describe protocols for investigating the immunomodulatory functions of PARP1 and PARP2.
  • To provide methodologies for studying PARP1 and PARP2's impact on the tumor microenvironment and immune surveillance.
  • To facilitate research into the dual roles of PARP1/PARP2 in cancer therapy and immune response.

Main Methods:

  • Utilizing established mouse tumor models.
  • Implementing protocols to assess protein poly-ADP-ribosylation in response to DNA damage.
  • Developing assays to evaluate the impact of PARP1 and PARP2 on immune cell infiltration and function within tumors.

Main Results:

  • The described protocols enable the study of PARP1/PARP2-mediated immunomodulation in vivo.
  • These methods allow for the characterization of how PARP inhibition affects the tumor immune microenvironment.
  • The findings support the investigation of PARPi beyond their direct cytotoxic effects, considering their influence on anti-tumor immunity.

Conclusions:

  • PARP1 and PARP2 possess significant immunomodulatory functions relevant to cancer progression.
  • Understanding these immunomodulatory roles is crucial for optimizing PARPi-based cancer therapies.
  • The presented protocols offer a framework for dissecting the complex interplay between PARP enzymes, DNA damage response, and anti-tumor immunity.
Keywords:
Flow cytometryImmune responseImmunohistochemistryPoly(ADP-ribose) polymerasesTumor microenvironment

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