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Tumor microenvironment dictates regulatory T cell phenotype: Upregulated immune checkpoints reinforce suppressive
Hye Ryun Kim1, Hyo Jin Park2, Jimin Son2
1Yonsei Cancer Center, Division of Medical Oncology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-Gu, Seoul, 120-752, South Korea.
Journal for Immunotherapy of Cancer
|December 6, 2019
Summary
Regulatory T (Treg) cells suppress anti-tumor immunity by upregulating immune checkpoint molecules in the tumor microenvironment (TME). Targeting these molecules, particularly PD-1 on Treg cells, may enhance cancer treatment efficacy.
Area of Science:
- Immunology
- Oncology
- Cancer Research
Background:
- Regulatory T (Treg) cells play a crucial role in cancer immunosuppression.
- The precise mechanisms of Treg cell-mediated immunosuppression within the tumor microenvironment (TME) remain incompletely understood.
Purpose of the Study:
- To investigate the phenotypic and functional changes of T cell subsets, focusing on immune checkpoint (IC) molecule expression on Treg cells within the TME.
- To elucidate the mechanisms by which the TME influences Treg cell immunosuppressive activity.
Main Methods:
- Comparative analysis of T cell phenotypes, including Treg cells, from peripheral blood, malignant effusions, and tumors in 103 cancer patients.
- Detailed examination of IC-molecule expression (PD-1, TIM-3, TIGIT, CTLA-4) on Treg and conventional T (Tconv) cells from paired blood, peritumoral, and tumor tissues in 12 lung cancer patients.
- Functional assays in a mouse lung cancer model to assess immunosuppressive mechanisms of tumor-infiltrating Treg cells.
Main Results:
- Immune checkpoint (IC) molecule expression, especially PD-1, was progressively upregulated on CD8+, CD4+, and Treg cells as they approached the tumor.
- PD-1 expression was significantly higher on Treg cells compared to Tconv cells in lung cancer patients and in a mouse model.
- PD-1 high-expressing tumor-infiltrating Treg cells exhibited potent immunosuppressive activity, partially reversible with anti-PD-1 antibody blockade.
Conclusions:
- The tumor microenvironment (TME) induces immunosuppressive functions in Treg cells through upregulation of immune checkpoint (IC) molecules.
- Targeting IC molecules, such as PD-1, on Treg cells presents a promising therapeutic strategy for enhancing anti-tumor immunity in cancer treatment.
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