Nasopharynx Battlefield: Cellular Immune Responses Mediated by Midkine in Nasopharyngeal Carcinoma and COVID-19

SIMPLE SUMMARY: One of the questions that experts are trying to answer about COVID-19 is whether it will have a positive or negative effect on cancer. It is important to consider the added risk of COVID-19 symptoms when making decisions about cancer treatments. To gain a deeper understanding of this, we discussed the relationship between COVID-19 and nasopharyngeal carcinoma (NPC), a type of cancer that, like COVID-19, initially causes inflammation in the nasopharynx. Specifically, we looked at the biomolecular variety and underlying intercellular ligand–receptor mechanisms through midkine (MK) signaling. We were astounded to discover how complex MK’s role is in the inflammatory response of these diseases, as it impacts the infiltration of immune cells into the inflamed microenvironment. This includes the abundance and interaction of immune cells, which can affect cancer progression and COVID-19 severity. As a result, exploring new cancer therapies that target MK gives hope of personalizing treatments for better outcomes. ABSTRACT: Clinical evidence suggests that the severe respiratory illness coronavirus disease 2019 (COVID-19) is often associated with a cytokine storm that results in dysregulated immune responses. Prolonged COVID-19 positivity is thought to disproportionately affect cancer patients. With COVID-19 disrupting the delivery of cancer care, it is crucial to gain momentum and awareness of the mechanistic intersection between these two diseases. This review discusses the role of the cytokine midkine (MK) as an immunomodulator in patients with COVID-19 and nasopharyngeal carcinoma (NPC), both of which affect the nasal cavity. We conducted a review and analysis of immunocellular similarities and differences based on clinical studies, research articles, and published transcriptomic datasets. We specifically focused on ligand–receptor pairs that could be used to infer intercellular communication, as well as the current medications used for each disease, including NPC patients who have contracted COVID-19. Based on our findings, we recommend close monitoring of the MK axis to maintain the desirable effects of therapeutic regimens in fighting both NPC and COVID-19 infections.