Curability difference between autochthonous mouse tumors and their transplants in association with immune gene

Hiroshi Tanooka1, Chie Kudo-Saito2, Fumiko Chiwaki3

  • 1Central Radioisotope Division, National Cancer Center Research Institute, Tokyo, Japan.

Plos One
|April 24, 2026
PubMed

Insights

Autochthonous tumors are harder to cure with radiation than transplanted tumors. Transplantation alters immune gene expression, impacting tumor curability and highlighting the importance of immune microenvironment in radiation therapy response.

Area of Science:

  • Immunology
  • Oncology
  • Cancer Research

Background:

  • Autochthonous (spontaneous) tumors are more resistant to radiation therapy than transplanted tumors in mice.
  • Understanding the immune microenvironment is crucial for improving cancer treatment efficacy.

Purpose of the Study:

  • To compare immune-related gene expression profiles between autochthonous and transplanted mouse fibrosarcomas.
  • To investigate the impact of tumor transplantation on immune gene expression and its relation to curability.

Main Methods:

  • Fibrosarcomas were induced by 3-methylcholanthrene (3MC) in mice.
  • Immune gene expression (Pd1, Pdl1, Pdl2, Cd3d, Cd8a, Cd8b, Ifnγ, Itga2, Gzmb, Foxp3) was analyzed in both autochthonous and transplanted tumors.
  • Tumor phenotypes and immune cell infiltration (DX5+ NK cells, CD8+ T cells) were assessed.

Main Results:

  • One non-transplantable tumor exhibited a benign phenotype with high levels of natural killer (NK) cells, CD8+ T cells, and Interferon-gamma (IFNγ) expression.
  • Transplantation of 11 tumors into syngeneic mice led to increased expression of immune genes including Programmed Death 1 (Pd1), Programmed Death Ligand 1 (Pdl1), Programmed Death Ligand 2 (Pdl2), Cluster of Differentiation 3 delta (Cd3d), Cluster of Differentiation 8 beta (Cd8b), and IFNγ.
  • Immune gene expression profiles differed significantly between autochthonous and transplanted tumors.

Conclusions:

  • Tumor transplantation significantly alters the immune gene expression profile.
  • Changes in immune gene expression following transplantation correlate with tumor transplantability and curability.
  • Immune gene expression status is a critical factor influencing the response of tumors to radiation therapy.