Related Experiment Video
Updated: Oct 4, 2025
Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
Published on: July 20, 2019
RNF2 ablation reprograms the tumor-immune microenvironment and stimulates durable NK and CD4+ T-cell-dependent
Zhuo Zhang1,2, Lin Luo3,4,5,6, Chuan Xing7,3
1Department of Radiation Oncology, University of Alabama at Birmingham School of Medicine, Hazelrig Salter Radiation Oncology Center, Birmingham, AL, USA. zhuophar@uab.edu.
Abstract:
Expanding the utility of immune-based cancer treatments is a clinical challenge due to tumor-intrinsic factors that suppress the immune response. Here we report the identification of tumoral ring finger protein 2 (RNF2), the core subunit of polycomb repressor complex 1, as a negative regulator of antitumor immunity in various human cancers, including breast cancer. In syngeneic murine models of triple-negative breast cancer, we found that deleting genes encoding the polycomb repressor complex 1 subunits Rnf2, BMI1 proto-oncogene, polycomb ring finger (Bmi1), or the downstream effector of Rnf2, remodeling and spacing factor 1 (Rsf1), was sufficient by itself to induce durable tumor rejection and establish immune memory by enhancing infiltration and activation of natural killer and CD4+ T cells, but not CD8+ T cells, into the tumor and enabled their cooperativity. These findings uncover an epigenetic reprogramming of the tumor-immune microenvironment, which fosters durable antitumor immunity and memory.
Insights
Tumor ring finger protein 2 (RNF2) suppresses antitumor immunity. Deleting RNF2 or related genes enhances immune cell infiltration, leading to durable tumor rejection and immune memory in breast cancer models.
Area of Science:
- Oncology
- Immunology
- Epigenetics
Background:
- Immune-based cancer treatments face challenges from tumor-intrinsic factors that suppress immune responses.
- Ring finger protein 2 (RNF2), a core subunit of polycomb repressor complex 1, is implicated in cancer progression.
Purpose of the Study:
- To investigate the role of tumoral RNF2 as a regulator of antitumor immunity.
- To explore the potential of targeting RNF2 for enhancing cancer immunotherapy.
Main Methods:
- Identification of RNF2 as a negative regulator of antitumor immunity in human cancers.
- Gene deletion studies of RNF2, BMI1, and RSF1 in syngeneic murine models of triple-negative breast cancer.
- Analysis of immune cell infiltration (NK, CD4+, CD8+ T cells) and activation within the tumor microenvironment.
Main Results:
- RNF2 acts as a negative regulator of antitumor immunity across various human cancers, including breast cancer.
- Deletion of RNF2, BMI1, or RSF1 genes in triple-negative breast cancer models induced durable tumor rejection.
- Enhanced infiltration and activation of natural killer and CD4+ T cells were observed, fostering immune memory.
Conclusions:
- Tumoral RNF2 is a key epigenetic regulator suppressing antitumor immunity.
- Targeting RNF2 and its pathway offers a novel strategy for epigenetic reprogramming of the tumor-immune microenvironment.
- This approach can enhance immune cell activity, leading to durable antitumor responses and immune memory.
Related Concept Videos
01:27Tumor Immunotherapy
01:27Cytotoxic T Cells-mediated Immune Response
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...