Related Experiment Video
Updated: Jun 16, 2026
Generation of Human Chimeric Antigen Receptor Regulatory T Cells
Published on: January 3, 2025
3-Methylcholanthrene-induced transforming growth factor-beta-producing carcinomas, but not sarcomas, are refractory
Kenji Chamoto1, Daiko Wakita, Takayuki Ohkuri
1Division of Immunoregulation, Section of Disease Control, Institute for Genetic Medicine, and Hokkaido University, Sapporo, Japan.
Abstract:
Regulatory T cells (Tregs) are major immunosuppressors in tumor-bearing hosts. Although Treg-depletion therapy has been shown to induce a complete cure in tumor-bearing mice, this treatment is not always successful. Using 3-methylcholanthrene-induced primary mouse tumors, we examined the distinct regulation of Treg-mediated immunosuppression between carcinomas and sarcomas. We showed that the number of Tregs was greatly increased in squamous cell carcinoma (SCC)-bearing mice compared with sarcoma-bearing mice. This appeared to be because SCC produced higher levels of active transforming growth factor (TGF)-beta, which is essential for inducing Tregs, compared with sarcoma. Moreover, SCC, but not sarcomas, were refractory to Treg-depletion therapy by treatment with anti-CD25 mAb. The refractoriness of SCC against Treg-depletion therapy was due to the rapid recovery of Tregs in SCC-bearing mice compared with sarcoma-bearing mice. However, combination treatment of anti-TGF-beta mAb with anti-CD25 mAb caused a significant reduction in Treg recovery and induced a complete cure in SCC-bearing mice. Thus, we showed the refractoriness of mouse carcinoma against Treg-depletion therapy using anti-CD25 mAb treatment. We also proposed a novel Treg-blocking combination therapy using anti-CD25 mAb and anti-TGF-beta mAb to induce a complete cure of tumor-bearing hosts.
Insights
Regulatory T cells (Tregs) suppress anti-tumor immunity. In mouse models, squamous cell carcinomas resisted Treg-depletion therapy, unlike sarcomas, due to rapid Treg recovery. Combination therapy targeting Tregs and TGF-beta achieved complete cures.
Area of Science:
- Immunology
- Oncology
- Cancer Research
Background:
- Regulatory T cells (Tregs) are key immunosuppressors in tumor-bearing hosts.
- Treg-depletion therapy shows promise but isn't always successful in eradicating tumors.
- Distinct Treg regulation mechanisms exist between different tumor types.
Purpose of the Study:
- To investigate the differential regulation of Treg-mediated immunosuppression in carcinomas versus sarcomas.
- To understand the refractoriness of squamous cell carcinoma (SCC) to Treg-depletion therapy.
- To develop an effective combination therapy for SCC-bearing hosts.
Main Methods:
- Utilized 3-methylcholanthrene-induced primary mouse tumors (carcinomas and sarcomas).
- Administered anti-CD25 mAb for Treg depletion and anti-TGF-beta mAb.
- Quantified Treg numbers and assessed tumor cure rates.
Main Results:
- SCC-bearing mice had significantly higher Treg numbers than sarcoma-bearing mice, linked to higher TGF-beta production by SCC.
- SCCs were refractory to anti-CD25 mAb treatment due to rapid Treg recovery.
- Combination therapy with anti-CD25 mAb and anti-TGF-beta mAb significantly reduced Treg recovery and cured SCC-bearing mice.
Conclusions:
- Mouse carcinoma exhibits refractoriness to Treg-depletion therapy with anti-CD25 mAb.
- A novel combination therapy using anti-CD25 mAb and anti-TGF-beta mAb effectively overcomes Treg-mediated immunosuppression.
- This combination therapy offers a potential strategy for achieving complete tumor eradication in hosts with carcinomas.
