Related Experiment Video
Updated: May 17, 2026

Induction of Murine Intestinal Inflammation by Adoptive Transfer of Effector CD4+CD45RBhigh T Cells into Immunodeficient Mice
Published on: April 21, 2015
Arid3b suppresses CD8 + T cell infiltration and function in microsatellite-stable colorectal cancer via Runx3
Shuo Wang1,2, Sen Hou1,2, Ce Luo3
1Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, China.
Abstract:
Microsatellite-stable/proficient mismatch repair (MSS/pMMR) colorectal cancer (CRC) is characterized by a cold tumor microenvironment, with limited CD8⁺ T cell infiltration and poor responsiveness to immune checkpoint inhibitors (ICIs). Here, using an in vivo CRISPR/Cas9 screen in a CMT93 cell-derived murine tumor model, we identify Arid3b as a key negative regulator of CD8⁺ T cell infiltration and antitumor activity. Genetic ablation of Arid3b in CD8⁺ T cells significantly enhances their intratumoral accumulation and promotes robust tumor control. Mechanistically, Arid3b deficiency upregulates Runx3, driving a tissue-resident memory-like phenotype and effector function. Notably, the benefits conferred by Arid3b deficiency are abrogated upon Runx3 deletion, indicating a RUNX3-dependent mechanism. Together, targeting ARID3B could offer a promising strategy to reshape the tumor microenvironment and sensitize MSS CRC to immunotherapy.
Insights
Targeting ARID3B in T cells enhances their infiltration into microsatellite-stable colorectal cancer (MSS CRC) tumors. This boosts anti-tumor activity and improves immunotherapy response in MSS CRC models.
Area of Science:
- Immunology
- Oncology
- Genetics
Background:
- Microsatellite-stable colorectal cancer (MSS CRC) exhibits a "cold" tumor microenvironment, hindering CD8+ T cell infiltration and limiting efficacy of immune checkpoint inhibitors (ICIs).
- Identifying novel regulators of T cell infiltration is crucial for overcoming immunotherapy resistance in MSS CRC.
Purpose of the Study:
- To identify key regulators of CD8+ T cell infiltration in MSS CRC.
- To explore the therapeutic potential of targeting these regulators to enhance anti-tumor immunity.
Main Methods:
- Conducted an in vivo CRISPR/Cas9 screen in a CMT93 cell-derived murine tumor model.
- Utilized genetic ablation of Arid3b in CD8+ T cells.
- Investigated the role of Runx3 in mediating the effects of Arid3b deficiency.
Main Results:
- Identified Arid3b as a critical negative regulator of CD8+ T cell infiltration and anti-tumor activity.
- Genetic ablation of Arid3b in CD8+ T cells significantly increased their accumulation within tumors and promoted tumor control.
- Arid3b deficiency upregulated Runx3, inducing a tissue-resident memory-like phenotype and enhancing effector function in a Runx3-dependent manner.
Conclusions:
- Targeting ARID3B in CD8+ T cells represents a promising strategy to enhance anti-tumor immunity in MSS CRC.
- Modulating ARID3B can reshape the tumor microenvironment, potentially sensitizing MSS CRC to immunotherapy.
Related Concept Videos
Inflammatory Bowel Disease III: Crohn's Disease
Abnormal Proliferation
Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Inhibition of Cdk Activity
Inhibition of CDK Activity
