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The double-edged role of interferon gamma in cancer immunity

Candelaria Aguilar-García1, Alejandra Martínez-Pérez1, Rocío Granda-Díaz2

  • 1Department of Functional Biology, Immunology, Universidad de Oviedo, Oviedo, Spain; Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Oviedo, Spain; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain.

International Review of Cell and Molecular Biology
|May 20, 2026
PubMed

Insights

Interferon-gamma (IFN-γ) is crucial for anti-tumor immunity, but its dysregulation in advanced cancers promotes tumor growth. Understanding IFN-γ

Area of Science:

  • Immunology
  • Oncology
  • Cancer Research

Background:

  • Interferon-gamma (IFN-γ) is a key cytokine in coordinating immune responses against viral and intracellular pathogens.
  • IFN-γ is essential for the anti-tumor activity of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells.
  • Dysregulated IFN-γ signaling in advanced tumors can promote cancer progression and immune evasion.

Purpose of the Study:

  • To elucidate the dual role of IFN-γ in cancer immunity.
  • To understand the conditions under which IFN-γ exhibits either anti-tumoral or pro-tumoral effects.
  • To address challenges in optimizing IFN-γ-based cancer therapies.

Main Methods:

  • Utilized knockout (KO) mouse models lacking IFN-γ.
  • Assessed the impact of IFN-γ deficiency on tumor cell elimination by CTLs and NK cells.
  • Investigated the effects of dysregulated IFN-γ signaling in advanced tumors.

Main Results:

  • IFN-γ knockout mice showed reduced CTL and NK cell-mediated tumor cell elimination.
  • Lack of IFN-γ led to accelerated tumor growth and metastasis in KO mice.
  • Dysregulated IFN-γ signaling in tumors confers protumoral and immunosuppressive functions.

Conclusions:

  • IFN-γ plays a critical role in regulating the anti-tumor immune response.
  • The dual role of IFN-γ in cancer (anti-tumoral vs. pro-tumoral) complicates its therapeutic application.
  • Further research is needed to delineate the specific contexts of IFN-γ's opposing roles for effective cancer therapy.
Keywords:
IFN-γT cellcancerpathway

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