Journal
ADVANCED SCIENCE
Volume 10, Issue 15, Pages -Publisher
WILEY
DOI: 10.1002/advs.202204514
Keywords
ferroptosis; head and neck cancer; programmed death ligand 1
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This study investigates the spatial association between the signatures of ferroptosis and inflammation/immune activation in head and neck squamous cell carcinoma (HNSCC). The study finds a stronger association between ferroptosis signature and inflammation/immune activation in HPV-negative HNSCC compared to HPV-positive ones. It is shown that ferroptotic stress induces PD-L1 expression through reactive oxygen species (ROS)-elicited NF-kappa B signaling pathway and calcium influx. Pre-treatment of murine HNSCC with ferroptosis inducers enhances the sensitivity of tumors to anti-PD-L1 antibody treatment.
As a type of immunogenic cell death, ferroptosis participates in the creation of immunoactive tumor microenvironments. However, knowledge of spatial location of tumor cells with ferroptosis signature in tumor environments and the role of ferroptotic stress in inducing the expression of immune-related molecules in cancer cells is limited. Here the spatial association of the transcriptomic signatures is demonstrated for ferroptosis and inflammation/immune activation located in the invasive front of head and neck squamous cell carcinoma (HNSCC). The association between ferroptosis signature and inflammation/immune activation is more prominent in HPV-negative HNSCC compared to HPV-positive ones. Ferroptotic stress induces PD-L1 expression through reactive oxygen species (ROS)-elicited NF-kappa B signaling pathway and calcium influx. Priming murine HNSCC with the ferroptosis inducer sensitizes tumors to anti-PD-L1 antibody treatment. A positive correlation between the ferroptosis signature and the active immune cell profile is shown in the HNSCC samples. This study reveals a subgroup of ferroptotic HNSCC with immune-active signatures and indicates the potential of priming HNSCC with ferroptosis inducers to increase the antitumor efficacy of immune checkpoint inhibitors.
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