Biologically driven cut-off definition of lymphocyte ratios in metastatic breast cancer and association with exosomal subpopulations and prognosis

被引:16
作者
Gerratana, Lorenzo [1 ,2 ,3 ]
Basile, Debora [1 ,3 ]
Toffoletto, Barbara [4 ]
Bulfoni, Michela [4 ]
Zago, Silvia [5 ]
Magini, Alessandro [6 ]
Lera, Marta [1 ]
Pelizzari, Giacomo [1 ,3 ]
Parisse, Pietro [7 ,8 ]
Casalis, Loredana [8 ]
Vitale, Maria Grazia [1 ,3 ]
Fanotto, Valentina [1 ,3 ]
Bonotto, Marta [3 ]
Caponnetto, Federica [1 ]
Bartoletti, Michele [1 ,3 ]
Lisanti, Camilla [1 ,3 ]
Minisini, Alessandro Marco [3 ]
Emiliani, Carla [6 ]
Di Loreto, Carla [1 ,4 ]
Fasola, Gianpiero [3 ]
Curcio, Francesco [1 ,5 ]
Beltrami, Antonio Paolo [1 ,4 ]
Cesselli, Daniela [1 ,4 ,9 ]
Puglisi, Fabio [1 ]
机构
[1] Univ Udine, Dept Med DAME, I-33100 Udine, Italy
[2] Northwestern Univ, Robert H Lurie ComprehensiveCancerCenter, Div Hematol & Oncol, Dept Med,Feinberg Sch Med, Chicago, IL 60611 USA
[3] ASUFC Univ Hosp, Dept Oncol, I-33100 Udine, Italy
[4] ASUFC Univ Hosp, Anat Pathol Inst, I-33100 Udine, Italy
[5] ASUFC Univ Hosp, Clin Pathol Inst, I-33100 Udine, Italy
[6] Univ Perugia, Dept Chem Biol & Biotechnol, I-06122 Perugia, Italy
[7] INSTM ST Unit, Area Sci Pk, I-34149 Trieste, Italy
[8] Elettra Sincrotrone Trieste SCpA, Area Sci Pk, I-34149 Trieste, Italy
[9] IRCCS, Dept Med Oncol, Ctr Riferimento Oncol CRO, I-33081 Aviano, Italy
关键词
CELLS; SURVIVAL; PROMOTE; DIFFERENTIATION; NEUTROPHILS; BIOGENESIS; EXPRESSION; PLATELET; BINDING; GROWTH;
D O I
10.1038/s41598-020-63291-2
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
High neutrophil to lymphocyte ratio (NLR) and monocyte to lymphocyte ratio (MLR) are respectively associated with systemic inflammation and immune suppression and have been associated with a poor outcome. Plasmatic exosomes are extracellular vesicles involved in the intercellular communication system that can exert an immunosuppressive function. Aim of this study was to investigate the interplay between the immune system and circulating exosomes in metastatic breast cancer (MBC). A threshold capable to classify patients according to MLR, NLR and PLR, was computed through a receiving operator curve analysis after propensity score matching with a series of female blood donors. Exosomes were isolated from plasma by ExoQuick solution and characterized by flow-cytometry. NLR, MLR, PLR and exosomal subpopulations potentially involved in the pre-metastatic niche were significantly different in MBC patients with respect to controls. MLR was significantly associated with number of sites at the onset of metastatic disease, while high levels of MLR and NLR were found to be associated with poor prognosis. Furthermore, exosomal subpopulations varied according to NLR, MLR, PLR and both were associated with different breast cancer subtypes and sites of distant involvement. This study highlights the nuanced role of immunity in MBC spread, progression and outcome. Moreover, they suggest potential interaction mechanisms between immunity, MBC and the metastatic niche.
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页数:19
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