Group Anna Martner
Myeloid leukemia occurs in two forms, the rapidly progressing acute myeloid leukemia (AML) and chronic myeloid leukemia (CML), in which leukemic cells expand slowly in bone-marrow and other blood-forming organs. AML and CML cells are frequently sensitive to the anti-leukemic functions of natural killer (NK) cells and T cells, and therapies aiming to boost the function of these cells may be useful in eradicating the leukemic clone. A major aim of our research is to define, utilizing a translational approach, the role of cytotoxic lymphocytes in AML and CML with focus on mechanisms of immunosuppression (oxygen radical production by leukemic cells, myeloid-derived suppressor cells) that may stifle the immune-mediated clearance of leukemic cells. The studies are, in part, based on our recent finding of a novel mechanism of immunosuppression in leukemia, in which myeloid leukemic cells produce reactive oxygen species (ROS) that kill adjacent NK cells and T cells by inducing apoptosis (Aurelius et al., Blood, 2012; Aurelius et al., J Leukocyte Biol, 2013). A parallel and related aim is to define mechanisms of differentiation of myeloid leukemic cells to form the basis for treatments that promote the maturation of leukemic cells into functional leukocytes.
A close collaboration with clinical units allow the recovery of primary leukemic cells, to be used for in vitro and in vivo studies. Furthermore, several leukemic animal models, including genetic leukemia models, transplantation models, and xenograft models, are being utilized in the studies.
Current Group Members
Anna Martner, PhD, Associate Professor
Frida Ewald Sander, PhD, Postdoc
Roberta Kiffin, PhD, Postdoc
Ebru Aydin, PhD student
Hanna Grauers Wiktorin, PhD student
Belson Rugwizangoga, PhD student
Junko Johansson, PhD student, associated
Alexander Hallner, PhD student, associated
- Ewald Sander, F., A. Rydström, E. Bernson, R. Kiffin, R. Riise, J. Aurelius, H. Anderson, M. Brune, R. Foà, K. Hellstrand, F. B. Thorén, A. Martner (2016) Dynamics of cytotoxic T cell subsets during immunotherapy predicts outcome in acute myeloid leukemia. Oncotarget, in press
- Martner, A., A. Rydström, R. E. Riise, J. Aurelius, M. Brune, R. Foa, K. Hellstrand, F. B. Thorén (2015) NK cell expression of natural cytotoxicity receptors may determine relapse risk in older AML patients undergoing immunotherapy for remission maintenance. Oncotarget, 6(40):42569-42574.
- Martner, A., H. G. Wiktorin, B. Lenox, F. Ewald Sander, E. Aydin, J. Aurelius, F. B. Thorén, A. Ståhlberg, S. Hermodsson, K. Hellstrand (2015) Histamine promotes the differentiation of dendritic cells and reduces tumor growth by targeting the myeloid NADPH oxidase. J. Immunol., 194: 5014-5021
- Ortiz, M. L.*, V. Kumar*, A. Martner*, S. Mony, L. Donthireddy, T. Condamine, J. Seykora, S. C. Knight, G. Malietzis, G. H. Lee, M. Moorghen, B. Lenox, N. Luetteke, E. Celis, and D. Gabrilovich (2015) Immature myeloid cells directly contribute to skin tumor development by recruiting IL-17-producing CD4+ T cells. J. Exp. Med. 212: 351-367.*shared first authorship
- Martner, A., F. Bergh Thorén, J. Aurelius, K. Hellstrand (2013) Immunotherapeutic strategies for relapse control in acute myeloid leukemia. Blood Reviews 27:209-16
- Ramachandran IR, A. Martner, A. Pisklakova, T. Condamine, T. Chase, T. Vogl, J. Roth, D. Gabrilovich, Y. Nefedova (2013) Myeloid-derived suppressor cells regulate growth of multiple myeloma by inhibiting T cells in bone marrow. J Immunol. 190: 3815-23
- Aurelius, J., A. Martner, M. Brune, L. Palmqvist, M. Hansson, K. Hellstrand, F.B. Thorén. (2012) Remission maintenance in acute myeloid leukemia: impact of functional histamine H2 receptors expressed by leukemic cells. Haematologica, 97:1904-1908
- Aurelius, J., F. B. Thoren, A. Akhiani, M. Brune, L. Palmqvist, M. Hansson, K. Hellstrand, and A. Martner. (2012) Monocytic AML cells inactivate anti-leukemic lymphocytes: role of NADPH oxidase/gp91phox expression and the PARP-1/PAR pathway of apoptosis. Blood 119: 5832-5837
- Thoren, F. B., J. Aurelius, and A. Martner. (2011) Antitumor properties of histamine in vivo. Nat Med 17:537; 537-538. (Commentary)
- Martner, A., J. Aurelius, A. Rydstrom, K. Hellstrand, and F. B. Thoren. (2011) Redox remodeling by dendritic cells protects antigen-specific T cells against oxidative stress. J Immunol 187:6243-6248