Abstract
ObjectivesAging is associated with altered immune function and chronic low‐grade inflammation, referred to as immunosenescence. As breast cancer is an age‐related disease, the impact of aging on tumor immune responses may have important consequences. However, effects of immunosenescence on breast tumor immune infiltration remain largely unknown.MethodsThis exploratory study investigated a broad panel of immune/senescence markers in peripheral blood and in the tumor microenvironment of young, middle‐aged and old patients diagnosed with early invasive luminal (hormone‐sensitive, HER2‐negative) breast cancer. In the old group, G8‐scores were computed as a correlate for clinical frailty.ResultsSignificant age‐related changes in plasma levels of several inflammatory mediators (IL‐1α, IP‐10, IL‐8, MCP‐1, CRP), immune checkpoint markers (Gal‐9, sCD25, TIM‐3, PD‐L1), IGF‐1 and circulating miRs (miR‐18a, miR‐19b, miR‐20, miR‐155, miR‐195 and miR‐326) were observed. Shifts were observed in distinct peripheral blood mononuclear cell populations, particularly naive CD8+ T‐cells. At the tumor level, aging was associated with lower total lymphocytic infiltration, together with decreased abundance of several immune cell markers, especially CD8. The relative fractions of cell subsets in the immune infiltrate were also altered. Clinical frailty was associated with higher frequencies of exhausted/senescent (CD27−CD28− and/or CD57+) terminally differentiated CD8+ cells in the blood and with increased tumor infiltration by FOXP3+ cells.ConclusionAging and frailty are associated with profound changes of the blood and tumor immune profile in luminal breast cancer, pointing to a different interplay between tumor cells, immune cells and inflammatory mediators at higher age.
Highlights
IntroductionAs the general population is ageing, the number of older patients with Breast cancer (BC) cancer is dramatically rising.[1] ageing might impact BC biology: compared to younger patients, older women often develop less aggressive tumors that are mostly oestrogen receptor (ER)-positive, lack over-expression of human epidermal growth factor receptor-2 (HER2) and have lower proliferation rates (luminal A-like tumors)
Breast cancer (BC), like all epithelial cancers, shows increased incidence with age
We examined the spatial distribution of the immune subtypes within the tumor and noted that, compared to the tumor centre, tumorinfiltrating lymphocytes (TILs) in the invasive front were significantly enriched in CD20+, cells which was seen by Ko€nig et al.,[17] while FOXP3+ cells tended to invade much deeper into the tumor core
Summary
As the general population is ageing, the number of older patients with BC cancer is dramatically rising.[1] ageing might impact BC biology: compared to younger patients, older women often develop less aggressive tumors that are mostly oestrogen receptor (ER)-positive, lack over-expression of human epidermal growth factor receptor-2 (HER2) and have lower proliferation rates (luminal A-like tumors). Lifelong exposure to endogenous and exogenous factors can induce progressive oxidative stress and DNA damage, eventually resulting in cell transformation and tumor initiation. Ageing is associated with accumulation of metabolically active senescent cells, exhibiting a senescence-associated secretory phenotype (SASP). SASP includes various inflammatory mediators that may promote tumor growth. Ageing induces a progressive decay of immune functioning, which may result in insufficient immune responses against a developing tumor.[2,3]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
