Immunomodulatory Effect of Green Tea Treatment in Combination with Low-dose Chemotherapy in Elderly Acute Myeloid Leukemia Patients with Myelodysplasia-related Changes

Author(s)

Calgarotto, Andrana K. ; Longhini, Ana L. ; Pericole de Souza, Fernando V. ; Duarte, Adriana S. Santos ; Ferro, Karla P. ; Santos, Irene ; Maso, Victor ; Olalla Saad, Sara T. ; Torello, Cristiane Okuda

• Document type: Journal article
• Source: INTEGRATIVE CANCER THERAPIES; v. 20, p. 12-pg., 2021-03-01.

Abstract

Green tea (GT) treatment was evaluated for its effect on the immune and antineoplastic response of elderly acute myeloid leukemia patients with myelodysplasia-related changes (AML-MRC) who are ineligible for aggressive chemotherapy and bone marrow transplants. The eligible patients enrolled in the study (n = 10) received oral doses of GT extract (1000 mg/day) alone or combined with low-dose cytarabine chemotherapy for at least 6 months and/or until progression. Bone marrow (BM) and peripheral blood (PB) were evaluated monthly. Median survival was increased as compared to the control cohort, though not statistically different. Interestingly, improvements in the immunological profile of patients were found. After 30 days, an activated and cytotoxic phenotype was detected: GT increased total and naive/effector CD8(+) T cells, perforin(+)/granzyme B+ natural killer cells, monocytes, and classical monocytes with increased reactive oxygen species (ROS) production. A reduction in the immunosuppressive profile was also observed: GT reduced TGF-beta and IL-4 expression, and decreased regulatory T cell and CXCR4(+) regulatory T cell frequencies. ROS levels and CXCR4 expression were reduced in bone marrow CD34(+) cells, as well as nuclear factor erythroid 2-related factor 2 (NRF2) and hypoxia-inducible factor 1 alpha (HIF-1 alpha) expression in biopsies. Immune modulation induced by GT appears to occur, regardless of tumor burden, as soon as 30 days after intake and is maintained for up to 180 days, even in the presence of low-dose chemotherapy. This pilot study highlights that GT extracts are safe and could improve the immune system of elderly AML-MRC patients. (AU)

• FAPESP's process: 12/06675-7 - Effects of Chlorella vulgaris and green tea extract (Camellia sinensis) in mice inoculated with myelocytic lineages P39 and HL-60
• Grantee: Andrana Karla Calgarotto
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 11/51959-0 - Biology of neoplastic diseases of bone marrow
• Grantee: Sara Teresinha Olalla Saad
• Support Opportunities: Research Projects - Thematic Grants