Nectins and Nectin-like (Necl) proteins are immunoglobulin-like adhesion molecules involved in cell–cell contact, synapse organization, and tissue integrity. In solid tumors, they also function as immune checkpoints by engaging activating and inhibitory receptors such as DNAM-1, TIGIT, CD96, and KIR2DL5A on T cells and NK cells. Altered expression, shedding, and localization of Nectins/Necls have been linked to immune escape, variable sensitivity to checkpoint blockade, and distinct clinical outcomes across tumor types. Despite increasing interest in this family, many aspects of their biology and therapeutic potential remain insufficiently defined.
This Research Topic aims to bring together new data on how Nectin and Nectin-like proteins shape anti-tumor immunity in solid cancers. A central focus is how individual ligands, particularly PVR/CD155 and related family members, integrate activating and inhibitory cues on cytotoxic lymphocytes and thereby influence response or resistance to current immunotherapies. Recent clinical setbacks with several TIGIT-targeting programs underscore the need to re-evaluate the hierarchy within the DNAM-1–PVR–TIGIT/CD96 axis and to clarify which ligands and receptors are dominant drivers of immune suppression in defined tumor settings. We seek studies that clarify mechanisms of Nectin/Necl-mediated immune regulation, define their roles in tumor progression and immune editing, and explore how these pathways can be targeted alone or in combination with PD-1/PD-L1, CTLA-4, and other agents. Contributions that connect molecular and cellular findings with in vivo models, biomarkers, and early clinical experience are especially encouraged, with the aim of refining the conceptual framework around the Nectin/Nectin-like axis in solid tumors.
We welcome the following submission types: Original Research, Case Report, Brief Research Report, and Editorial
• Regulation and pattern of Nectin/Nectin-like expression in solid tumors and their microenvironment • Receptor–ligand interactions of Nectins/Necls with DNAM-1, TIGIT, CD96, KIR2DL5A and downstream signaling in T, NK and myeloid cells • Preclinical models defining how Nectin/Necl pathways contribute to immune suppression, tumor growth, or sensitivity to immune responses and immunotherapy • Design and characterization of therapeutic approaches (e.g., antibodies, bispecifics, fusion proteins, ADCs) targeting Nectin/Necl pathways • Biomarker strategies using Nectin/Necl expression or function to guide patient selection and monitor treatment response • Translational and early clinical data involving Nectin/Necl-targeted agents or rational immunotherapy combinations in solid tumors
Authors are invited to submit mechanistic, translational, and clinically oriented work that advances understanding of Nectin and Nectin-like proteins as immune regulators and therapeutic targets in solid tumors.
Article types and fees
This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:
Brief Research Report
Case Report
Classification
Clinical Trial
Editorial
FAIR² Data
FAIR² DATA Direct Submission
General Commentary
Hypothesis and Theory
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Article types
This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:
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