New Treatment for Severe Cancer Patients with Chemotherapy Resistance Developed

KAIST, Experiment Removing Regulatory T Cells within Tumors
Significant Improvement in Anticancer Drug Efficacy

Domestic researchers have developed a cancer immunotherapy that selectively removes regulatory T cells present within tumors, which inhibit the ability of immune cells to eliminate cancer cells. This is evaluated as a new treatment strategy for patients with intractable cancers who show resistance to existing immune checkpoint inhibitor therapies.

KAIST announced on the 6th that a research team led by Professor Suhyung Park from the Graduate School of Medical Science and Engineering at KAIST, in collaboration with Professor Shin Eui-cheol of KAIST and Professors Seong-il Seo and Min-yong Kang from Samsung Medical Center, proposed a new immuno-oncology strategy through the selective removal of regulatory T cells within tumors.

In our body, regulatory T cells play a role in controlling excessive immune responses and suppressing the occurrence of autoimmune diseases. The research team discovered a new target protein called Siglec-1 (hereafter CEACAM1) that enables the selective removal of regulatory T cells present only within tumors without affecting other regulatory T cells. They demonstrated that targeting this protein to selectively remove tumor-infiltrating regulatory T cells significantly enhances the efficacy of existing immune checkpoint inhibitors widely used in cancer patients.

The development of therapies that selectively remove regulatory T cells within tumors is a major interest among many cancer researchers. To selectively remove tumor-infiltrating regulatory T cells, it is necessary to identify a target protein that is specifically and highly expressed only on these cells.

The research team analyzed tissues and blood samples obtained from kidney cancer patients and found that CEACAM1 is not expressed on regulatory T cells present in the blood but is selectively expressed on regulatory T cells within tumors. Furthermore, analysis of single-cell transcriptome data confirmed that this pattern is not limited to kidney cancer but appears in various cancer types. When tumor-infiltrating regulatory T cells expressing CEACAM1 were removed from the immune cells of kidney cancer patients, a remarkable increase in the tumor-eliminating ability of immune cells responsible for immuno-oncology was observed. Additionally, by removing immune cells expressing CEACAM1, the immuno-oncology function of immune checkpoint inhibitors, a representative immune checkpoint inhibitor, was significantly enhanced.

Based on these results, the research team revealed that tumor-infiltrating regulatory T cells expressing CEACAM1 are the main cells suppressing anti-tumor immune responses. Understanding the detailed characteristics of these cells and selectively removing them or targeting them is expected to be utilized in the development of highly effective anticancer therapies and immunotherapeutics.

The research team stated, "This study is important in that it not only discovered a new target protein but also enhanced the understanding of the biological characteristics of tumor-infiltrating regulatory T cells," adding, "Ultimately, it is expected to be a solution to overcome resistance to immune checkpoint inhibitors."

The results of this study were recently published in Clinical Cancer Research, a journal in the field of oncology published by the American Association for Cancer Research.

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