Age-related remodelling of the blood immunological portrait and the local tumor immune response in patients with luminal breast cancer

被引:33
作者
Berben, Lieze [1 ]
Floris, Giuseppe [2 ,3 ]
Kenis, Cindy [4 ]
Dalmasso, Bruna [5 ,6 ]
Smeets, Ann [7 ]
Vos, Hanne [7 ]
Neven, Patrick [8 ]
Martinez, Asier Antoranz [3 ]
Laenen, Annouschka [9 ]
Wildiers, Hans [1 ,10 ]
Hatse, Sigrid [1 ]
机构
[1] Katholieke Univ Leuven, Lab Expt Oncol, Dept Oncol, Leuven, Belgium
[2] Univ Hosp Leuven, Dept Pathol, Leuven, Belgium
[3] Katholieke Univ Leuven, Lab Translat Cell & Tissue Res, Dept Imaging & Pathol, Leuven, Belgium
[4] Univ Hosp Leuven, Dept Gen Med Oncol & Geriatr Med, Leuven, Belgium
[5] Univ Genoa, Dept Internal Med & Med Specialties DiMI, Genetis Rare Canc, Genoa, Italy
[6] IRCCS Osped Policlin San Martino, Genoa, Italy
[7] Katholieke Univ Leuven, Dept Surg Oncol, Univ Hosp Leuven, Leuven, Belgium
[8] Univ Hosp Leuven, Dept Gynaecol & Obstet, Leuven, Belgium
[9] Interuniv Ctr Biostat & Stat Bioinformat, Leuven, Belgium
[10] Univ Hosp Leuven, Dept Gen Med Oncol, Leuven, Belgium
关键词
ageing; biomarkers; breast cancer; clinical frailty; tumor immune infiltrate; SCREENING TOOLS; T-CELLS; IMMUNOSENESCENCE; HOMEOSTASIS; EXPRESSION; BIOMARKERS; MICRORNAS; CARCINOMA; CYTOKINES; CLUSTER;
D O I
10.1002/cti2.1184
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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-1 alpha, 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.
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页数:22
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