Natural cancer-killing activity of human granulocytes

Abstract

Natural existence of cancer killing activity (CKA) predominantly in granulocytes was first discovered in the cancer-resistant mice (SR/CR mice) and later in humans. The in vitro assay conditions for CKA are different from the conventional cytotoxicity assays. An experimental therapy based on the transfusion of the collected human granulocytes from the healthy donors as the direct therapeutic agent was conceptualized previously. In this perspective, the findings of our ongoing studies are summarized in hope to help clinicians who may be interested in testing the efficacy of donor granulocytes for treating cancer. Granulocyte CKA is expected to play a protective role against cancers in humans and is affected by factors, such as age, stress, seasonality, nutrients, BCG and irradiation etc. Based on our recent findings that all the target cells tested so far have negative charges on the surface whereas normal cells are charge-neutral on the surface, we propose that the negative surface charge is the cellular property targeted by granulocytes which are the only cells with positively-charged surfaces.

Ginsenoside Rg1 as a promising adjuvant agent for enhancing the anti-cancer functions of granulocytes inhibited by noradrenaline

“…Among the 32 downregulated genes, 8 genes were distributed in environmental information processing, 10 genes in human diseases, 4 genes in metabolism, and 10 genes in organismal systems. In our previous studies, the granulocyte-mediated killing of cancer cells was roughly divided into 3 stages: chemotaxis, recognition, and killing ( 28 , 44 ). Therefore, we considered that factors related to cell migration, cell adhesion, cytoskeleton composition, cell proliferation and apoptosis, and immune response may all be associated with the immunoprotective effect of ginsenoside Rg1 on granulocytes inhibited by NA.…”

Photosensitizer-Laden Neutrophils Are Controlled Remotely for Cancer Immunotherapy

“…The TKA of optically activated NE P s was decreased toward HUVECs. A previous study shows that NEs can differentiate malignant cells through cell surface charges (Le and Cui, 2018). The abundant negative charges on the cellular surface of tumor cells (Chen et al, 2016) makes Tumor Accumulation via the Inherent Chemotactic Migration Ability of NEs For in vivo tumor killing, reinfusion and the subsequent tumor accumulation of nano-photosensitizer-laden NEs were the crucial steps.…”

“…(2) NE transfusion has been in clinical use for decades to treat infections and is the only allogeneic leukocyte transfusion used as a standard therapy (Pagano et al, 2018); therefore, the regulatory requirements for clinical use of our design may have a shortcut. (3) NE transfusion has also shown potential in tumor immunotherapy by taking advantage of their natural killing effect (although highly variable between sources; Le and Cui, 2018). (4) Healthy NEs have been shown to rapidly migrate to cancer lesions via cancer cell-induced chemotaxis (Kolaczkowska and Kubes, 2013;Xue et al, 2017).…”