The canonical Notch pathway is based on a conserved signal transduction machinery that, in mammals, begins with the interaction between receptors (Notch-1 to -4) and ligands (Jagged-1 and -2 or Delta like (Dll)-1, -3 and -4), normally expressed on neighboring cells. Then, three sequential cleavages result in the release of the Notch intracellular domain that translocates into nucleus, interacts with the DNA binding protein CSL/RBP-Jk and promotes the transcription of target genes. The activation of Notch signaling influences the biology of many cell types, including cells of the immune system, through the control of crucial biologic processes, such as survival, proliferation, differentiation and tissue homeostasis. The outcome of Notch signaling is highly context dependent due to the many levels of regulation involved. Not surprisingly, the aberrant modulation of the Notch pathway, either positive or negative, is involved in the development of different types of solid tumors and hematologic malignancies in which the role of Notch can be either oncogenic or tumor suppressive.

In the past, many efforts have focused on the dissection of the role of Notch in tumor onset and progression. More recently, accumulating evidence suggests a pivotal role of Notch signaling in the cross-talk between tumor cells and the microenvironment. However, the effects of Notch signaling on tumor immune responses and immune surveillance remain largely unexplored. The interactions between Notch, tumor cells, the tumor environment and immune system may influence the progression and the outcome of neoplastic processes and likely represent new targets of tailored cancer therapies.

This Research Topic will focus on the description of the mechanisms through which the modulation of Notch signaling in tumor cells and/or in components of the tumor environment may impact on the behavior of cell subsets involved in the adaptive and innate immune response, and subsequently, on their responses against the tumor, either favoring or limiting cancer cell growth and expansion.

We welcome the submission of Original Research and Review articles that cover, but are not limited, to the following topics:

1. Notch and effector T cell response in cancer;
2. Notch and MDSC response in cancer;
3. Notch and regulatory T cell response in cancer;
4. Notch and B cell response in cancer;
5. Notch and NK cell response in cancer;
6. Notch and myeloid cell subset response in cancer;
7. Notch and cancer immunotherapies;
8. Notch, inflammation and cancer;
9. Notch, chemokines and cancer.

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Frontiers in Immunology

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