IMR Press / FBL / Volume 28 / Issue 1 / DOI: 10.31083/j.fbl2801002
Open Access Commentary
Alternative Chemotherapies: Angiotensin-Converting Enzyme Inhibitors Reduce Myeloid-Derived Suppressor Cells to Benefit Older Patients with Colorectal Cancer
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1 Department of Microbiology Immunology and Parasitology, UNIFESP, 04023-0900 São Paulo, Brazil
2 Department of Medicine, Division of Gastrointestinal Oncology, UNIFESP, 04023-0900 São Paulo, Brazil
3 Department of Immunology, University of Tübingen, 72074 Tübingen, Germany
4 Health Sciences North Research Institute, Sudbury, ON P3E 2H3, Canada
*Correspondence: vbueno@unifesp.br (Valquiria Bueno)
Academic Editor: Mateusz Maciejczyk
Front. Biosci. (Landmark Ed) 2023, 28(1), 2; https://doi.org/10.31083/j.fbl2801002
Submitted: 4 November 2022 | Revised: 22 December 2022 | Accepted: 28 December 2022 | Published: 9 January 2023
Copyright: © 2023 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.
Abstract

Older individuals are more likely to develop solid cancers, but at the same time are more sensitive to the side effects of chemotherapy. In addition, older adults are more likely to present with chronic diseases (comorbidities) and immunosenescence that may decrease immunosurveillance against cancer. Clinical outcomes for the older patient with cancer are different from the younger patient and require different research and treatment approaches. Thus, alternative therapeutic approaches tailored specifically to the older patients are required. Colorectal cancer (CRC) has a high incidence in older individuals and is the third leading cause of cancer death globally. Anti-hypertensives are used by a large proportion of older patients and some studies have pointed to a positive impact of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) on CRC outcomes. As we have previously shown in a mouse model, lung metastases express ACE and contain many infiltrating myeloid-derived suppressor cells (MDSC); particularly high levels of MDSC are also present in the blood of older patients with CRC and other cancers, and are associated with disease severity. In this Commentary, we hypothesize that one mechanism responsible for the positive impact of ACEi or ARB on the outcome of CRC is the modulation of myeloid cells contributing to their maturation to non-suppressive neutrophils/monocytes and diverting them away from retaining an immature MDSC phenotype.

Keywords
longevity
comorbidities
colorectal cancer
immunosenescence
myeloid-derived suppressor cells
angiotensin-converting enzyme
Funding
88881.310735/2018-01/CAPES PrInt UNIFESP
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