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Eosino-philia for cancer: the hidden ancient weapon rises up

Eosinophils are white blood cells that secrete powerfully destructive proteins.Major basic protein 1 and 2 (MBP-1, MBP-2), eosinophil-derived neurotoxin (EDN), and eosinophil peroxidase all are cytotoxic proteins. EPO EPO catalyzes the oxidation of halides (chlorine, iodine) and nitric oxide to form reactive oxygen and nitrogen species (ROS/RNS), which can promote oxidative stress and subsequent cell death. These protein may have played an evolutionary role in combatting parasites; today they are responsible for chronic asthma and modern allergies. Eosinophil cationic protein (ECP) is a very powerful cellular toxin besides a parasite killer. But now that most people, particularly in the West, enjoy good hygiene and few parasites, the eosinophils have become destructive agents, causing allergies and asthma. Multiple studies have shown an improved prognosis with tumor-associated tissue eosinophilia (TATE) or evidence of eosinophil degranulation in various types of solid tumors, including colon tumors, oral squamous cell carcinoma, esophageal cancer, nasopharyngeal carcinoma, lung adenocarcinoma, bladder carcinoma and prostate cancer.

A new research theorized that since eosinophils are capable of killing parasites and can cause damage in the lungs of asthma patients, they might play a role in cancer treatment and would be able to kill tumor cells. A new study from Tel Aviv University finds that eosinophils may be used to eliminate malignant colon cancer cells. The research was led by Prof. Ariel Munitz of the Department of Microbiology and Clinical Immunology at TAU’s Sackler School of Medicine in collaboration with colleagues in Tel Aviv Medical Center’s Gastroenterology Department. The largest eosinophil reservoir is situated in the digestive system, so the researchers initially decided to test their theories on colon cancer. In the first stage of research, they selected samples from tumors of 275 patients to determine the number of eosinophils in a tumor as compared with the stage and severity of the disease. The researchers subsequently tested their hypotheses in various mouse models of colorectal cancer. They discovered that eosinophils displayed potent anti-tumor activities and could directly kill tumor cells: the higher the number of eosinophils in the tumor, the less severe the disease, which represents a clear correlation.

Using adoptive transfer and cytokine neutralization experiments, we demonstrate that the tumor microenvironment supported prolonged survival of these cells independently of IL-5, a cytokine that tipically promotes eosinophil survival. Scientists also found that when eosinophils were activated by interferon (IFN)-gamma, that induced an even greater tumor-killing response. Following various extensive analyses, the team concluded that eosinophils have unique and distinct activities in comparison with other cells present in the tumor. For example, thay can kill tumors independently of cytotoxic T lymphocytes. The fact that eosinophils represent a distinct weapon in fighting tumor cells opens new avenues for treatment of cancer, either by encouraging eosinophils to unleash their robust anti-tumor response, or by combining treatments to harness the potent forces of both eosinophils and cytotoxic T cells. This fact has enormous implications for cancer immunotherapy. Eosinophils are rare white blood cells, making up less than 1% of the total number of granulocytes occurring in the human body. But this could be not exceedingly important, since their cytotoxic potential is really huge. There is only a need to recruit this potential and specifically committit it toward the “enemy” cancer. 

This interesting research is published in the journal Cancer Immunology Research.

  • Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.

Scientific references

Reichman H et al. Cancer Immunol Res. 2019 Jan 21.

Inoue M et al. Oncol Lett. 2016 Dec; 12(6):5269-5274.

Sakkal S et al. Curr Med Chem. 2016; 23(7):650-66.

Gatault S et l. J Immunol. 2015 Sep; 195(5):2483-92.

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Dott. Gianfrancesco Cormaci
Dott. Gianfrancesco Cormaci
Laurea in Medicina e Chirurgia nel 1998, specialista in Biochimica Clinica dal 2002, ha conseguito dottorato in Neurobiologia nel 2006. Ex-ricercatore, ha trascorso 5 anni negli USA alle dipendenze dell' NIH/NIDA e poi della Johns Hopkins University. Guardia medica presso la casa di Cura Sant'Agata a Catania. In libera professione, si occupa di Medicina Preventiva personalizzata e intolleranze alimentari. Detentore di un brevetto per la fabbricazione di sfarinati gluten-free a partire da regolare farina di grano. Responsabile della sezione R&D della CoFood s.r.l. per la ricerca e sviluppo di nuovi prodotti alimentari, inclusi quelli a fini medici speciali.

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