AUTHOR=Sultana Jasmine , Choudhury Pritha Roy , Bera Saurav , Chakravarti Mohona , Guha Aishwarya , Das Prodipto , Das Juhina , Iyer Gayatri S , Sarkar Anirban , Dhar Sukanya , Ganguly Nilanjan , Baral Rathindranath , Bose Anamika , Banerjee Saptak 

TITLE=Notch signalling in T cells: bridging tumour immunity and intratumoral cellular crosstalk

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1659614

DOI=10.3389/fimmu.2025.1659614

ISSN=1664-3224

ABSTRACT=BackgroundNotch 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 contentNotch 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.ConclusionThis 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.