Natural killer cell cytotoxicity is a predictor of outcome for patients with high risk myelodysplastic syndrome and oligoblastic acute myeloid leukemia treated with azacytidine

被引：14

作者：

Tsirogianni, Maria ^{[1
]}

Grigoriou, Eirini ^{[2
]}

Kapsimalli, Violetta ^{[3
]}

Dagla, Kleopatra ^{[4
]}

Stamouli, Maria ^{[4
]}

Gkirkas, Konstantinos ^{[4
]}

Konsta, Eve ^{[4
]}

Karagiannidou, Angeliki ^{[4
]}

Gkodopoulos, Konstantinos ^{[4
]}

Stavroulaki, Georgia ^{[4
]}

Pappa, Vassiliki ^{[4
]}

Angelopoulou, Maria ^{[5
]}

Lowdell, Mark ^{[6
]}

Tsirigotis, Panagiotis ^{[4
]}

机构：

[1] St Savvas Reg Canc Hosp, Dept Hematol & Bone Marrow Transplantat, Athens, Greece

[2] Evangelismos Gen Hosp, Dept Immunol & Histocompatibil, Athens, Greece

[3] Univ Athens, Sch Med, Dept Microbiol, Athens, Greece

[4] Univ Athens, ATTIKO Gen Univ Hosp, Dept Internal Med 2, Hematol Div, Rimini 1, Athens 12462, Greece

[5] Univ Athens, Laikon Gen Hosp, Dept Hematol & Bone Marrow Transplantat, Athens, Greece

[6] Royal Free Hosp, Inst Immun & Transplantat, Ctr Cell Gene & Tissue Therapeut, London, England

来源：

LEUKEMIA & LYMPHOMA | 2019年 / 60卷 / 10期

关键词：

Natural killer cell; NK-cytotoxicity; azacytidine; myelodysplastic syndrome; acute myeloid leukemia; CONVENTIONAL CARE REGIMENS; REGULATORY T-CELLS; NK CELLS; EXPRESSION; SURVIVAL; EFFICACY; MDS;

D O I：

10.1080/10428194.2019.1581935

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The aim of the present study was to identify biomarkers predictive of the outcome of patients with high-risk myelodysplastic syndrome and oligoblastic acute myeloid leukemia (AML) treated with 5-azacytidine (AZA). We prospectively examined the association between NK-cytotoxic activity, myeloid-derived suppressor cells (MDSCs), and T-regulatory cells (Tregs) on the overall survival (OS) of patients. Patients with NK-cytotoxicity above a critical threshold had a longer duration of response and survived longer than patients with severe impairment of NK-cytotoxicity. The numbers of MDSCs, and Tregs in the PB of patients after a short exposure to AZA were not different from normal donors. In conclusion, the results of our study suggest that the therapeutic activity of AZA is at least partly mediated by an immunomodulatory effect. To our knowledge, this is the first study reported so far, that shows a positive correlation between NK cytotoxicity and OS of AZA-treated patients.

引用

页码：2457 / 2463

页数：7

共 20 条

[1] Increased production of immature myeloid cells in cancer patients: A mechanism of immunosuppression in cancer
Almand, B
Clark, JI
Nikitina, E
van Beynen, J
English, NR
Knight, SC
Carbone, DP
Gabrilovich, DI
[J]. JOURNAL OF IMMUNOLOGY, 2001, 166 (01) : 678 - 689
[2] Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards
Bronte, Vincenzo
Brandau, Sven
Chen, Shu-Hsia
Colombo, Mario P.
Frey, Alan B.
Greten, Tim F.
Mandruzzato, Susanna
Murray, Peter J.
Ochoa, Augusto
Ostrand-Rosenberg, Suzanne
Rodriguez, Paulo C.
Sica, Antonio
Umansky, Viktor
Vonderheide, Robert H.
Gabrilovich, Dmitry I.
[J]. NATURE COMMUNICATIONS, 2016, 7
[3] Reduced DNAM-1 expression on bone marrow NK cells associated with impaired killing of CD34+ blasts in myelodysplastic syndrome
Carlsten, M.
Baumann, B. C.
Simonsson, M.
Jadersten, M.
Forsblom, A-M
Hammarstedt, C.
Bryceson, Y. T.
Ljunggren, H-G
Hellstrom-Lindberg, E.
Malmberg, K-J
[J]. LEUKEMIA, 2010, 24 (09) : 1607 - 1616
[4] Phenotypic alterations, clinical impact and therapeutic potential of regulatory T cells in cancer
Chaudhary, Belal
Abd Al Samid, May
al-Ramadi, Basel K.
Elkord, Eyad
[J]. EXPERT OPINION ON BIOLOGICAL THERAPY, 2014, 14 (07) : 931 - 945
[5] Induction of myelodysplasia by myeloid-derived suppressor cells
Chen, Xianghong
Eksioglu, Erika A.
Zhou, Junmin
Zhang, Ling
Djeu, Julie
Fortenbery, Nicole
Epling-Burnette, Pearlie
Van Bijnen, Sandra
Dolstra, Harry
Cannon, John
Youn, Je-in
Donatelli, Sarah S.
Qin, Dahui
De Witte, Theo
Tao, Jianguo
Wang, Huaquan
Cheng, Pingyan
Gabrilovich, Dmitry I.
List, Alan
Wei, Sheng
[J]. JOURNAL OF CLINICAL INVESTIGATION, 2013, 123 (11) : 4595 - 4611
[6] Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia
Cheson, Bruce D.
Greenberg, Peter L.
Bennett, John M.
Lowenberg, Bob
Wijermans, Pierre W.
Nimer, Stephen D.
Pinto, Antonio
Beran, Miloslav
de Witte, Theo M.
Stone, Richard M.
Mittelman, Moshe
Sanz, Guillermo F.
Gore, Steven D.
Schiffer, Charles A.
Kantarjian, Hagop
[J]. BLOOD, 2006, 108 (02) : 419 - 425
[7] Reduced natural killer (NK) function associated with high-risk myelodysplastic syndrome (MDS) and reduced expression of activating NK receptors
Epling-Burnette, Pearlie K.
Bai, Fanqi
Painter, Jeffrey S.
Rollison, Dana E.
Salih, Helmut R.
Krusch, Matthias
Zou, JianXiang
Ku, Edna
Zhong, Bin
Boulware, David
Moscinski, Lynn
Wei, Sheng
Djeu, Julie Y.
List, Alan F.
[J]. BLOOD, 2007, 109 (11) : 4816 - 4824
[8] Fazekas de St Groth B, 2011, METHODS MOL BIOL, V707, P263, DOI 10.1007/978-1-61737-979-6_17
[9] Azacitidine Prolongs Overall Survival Compared With Conventional Care Regimens in Elderly Patients With Low Bone Marrow Blast Count Acute Myeloid Leukemia
Fenaux, Pierre
Mufti, Ghulam J.
Hellstrom-Lindberg, Eva
Santini, Valeria
Gattermann, Norbert
Germing, Ulrich
Sanz, Guillermo
List, Alan F.
Gore, Steven
Seymour, John F.
Dombret, Herve
Backstrom, Jay
Zimmerman, Linda
McKenzie, David
Beach, C. L.
Silverman, Lewis R.
[J]. JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (04) : 562 - 569
[10] Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study
Fenaux, Pierre
Mufti, Ghulam J.
Hellstrom-Lindberg, Eva
Santini, Valeria
Finelli, Carlo
Giagounidis, Aristoteles
Schoch, Robert
Gattermann, Norbert
Sanz, Guillermo
List, Alan
Gore, Steven D.
Seymour, John F.
Bennett, John M.
Byrd, John
Backstrom, Jay
Zimmerman, Linda
McKenzie, David
Beach, C. L.
Silverman, Lewis R.
[J]. LANCET ONCOLOGY, 2009, 10 (03) : 223 - 232

← 1 2 →