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Tumor Transplantation for Assessing the Dynamics of Tumor-Infiltrating CD8+ T Cells in Mice
Published on: June 12, 2021
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.
Abstract:
Compared with transplanted tumors, autochthonous tumors are difficult to cure using experimental radiation therapy in mice. Here we analyzed differences in immune-related gene expression profiles between mouse fibrosarcomas subcutaneously induced by 3-methylcholanthrene (3MC) and their corresponding transplanted tumors. The immune genes examined were Pd1, Pdl1, Pdl2, Cd3d, Cd8a, Cd8b, Ifnγ, Itga2, Gzmb, and Foxp3. Among 12 tumors, one was non-transplantable and showed a benign phenotype with an abundance of DX5+ natural killer cells and CD8+ T cells together with increased IFNγ expression and mRNA levels of all immune genes except for Itga2. The other 11 transplantable tumors showed increased expression of Pd1, Pdl1, Pdl2, Cd3d, Cd8b, and Ifnγ following transplantation into syngeneic mice. These effects of transplantation highlight the relevance of immune gene expression status to the curability of tumors.
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.

