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Updated: Jan 14, 2026
Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells
Published on: March 7, 2025
Notch signalling in T cells: bridging tumour immunity and intratumoral cellular crosstalk
Jasmine Sultana1, Pritha Roy Choudhury1, Saurav Bera1
1Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute (CNCI), Kolkata, India.
Background:
Notch receptor-ligand interaction is ubiquitous and fundamental for coordinating cellular differentiation and determining cell fate for the development of various tissues and organs. Aberrant mutations in the Notch cascade result in various pathophysiological disorders, including cancer. Diverse aspects of carcinogenesis regulated by Notch include the shaping of anti-tumour T-cell immunity through antigen-presenting cell (APC)-T cell interaction and effector functions.
Chief Content:
Notch depends on juxtacrine and paracrine signalling to influence intercellular communications in the tumour microenvironment. Several preclinical and clinical studies have revealed Notch as a bi-effector molecule, which has a differential effect depending on the immune contexture of the tumour microenvironment. The Notch cascade serves as an effective therapeutic target in preventing off-target cell death and promoting tumour-specific T-cell priming.
Conclusion:
This review revolves around Notch crosstalk with respect to the interaction between T-cell populations and other intratumoral cellular components, including professional antigen-presenting cells like dendritic cells, macrophages, B cells, immunosuppressive myeloid-derived suppressor cells, and cancer stem cells. It also summarizes the impact of targeting Notch signalling within intratumoral T cells in combination with traditional oncotherapies.
Insights
Notch signaling coordinates cell fate and influences anti-tumor immunity. Targeting Notch pathways offers a promising strategy for cancer therapy by modulating T-cell responses within the tumor microenvironment.
Area of Science:
- Immunology
- Cell Biology
- Cancer Research
Background:
- Notch receptor-ligand interactions are crucial for cell differentiation and fate determination during development.
- Dysregulation of the Notch pathway is implicated in various diseases, including cancer.
- Notch signaling impacts anti-tumor T-cell immunity and effector functions via antigen-presenting cell (APC)-T cell interactions.
Purpose of the Study:
- To review Notch signaling's role in intercellular communication within the tumor microenvironment.
- To explore Notch as a bi-effector molecule with context-dependent effects on tumor immunity.
- To highlight Notch as a therapeutic target for enhancing anti-tumor responses.
Main Methods:
- Review of preclinical and clinical studies on Notch signaling in cancer.
- Analysis of Notch pathway's influence on T-cell populations and other intratumoral cells.
- Examination of Notch crosstalk with antigen-presenting cells, myeloid-derived suppressor cells, and cancer stem cells.
Main Results:
- Notch signaling modulates intercellular communication in the tumor microenvironment through juxtacrine and paracrine signaling.
- Notch exhibits differential effects on tumor immunity based on the microenvironment's immune contexture.
- Targeting Notch can prevent off-target cell death and promote tumor-specific T-cell priming.
Conclusions:
- Notch signaling is a key regulator of T-cell interactions and immune cell crosstalk within tumors.
- Targeting Notch in combination with conventional therapies may enhance anti-cancer efficacy.
- Understanding Notch crosstalk is vital for developing novel cancer immunotherapies.
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