Andreas Lundqvist's Group

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Tumor immunology

Our research focuses to develop novel immunotherapy regimens for patients with cancer.

The immune system plays an important role to prevent local growth and dissemination of cancer. Therapies based on activating the immune system, in particular T and NK cells, result in beneficial responses in patients with cancer. However, the majority of patients fail to respond to immunotherapy. In order to harness the full potential of the immune system T and NK cells need to colonize tumors as well as to display optimal tumor killing potential. In several projects, we investigate the ability of T and NK cells to migrate towards tumors, to persist within the tumor microenvironment, and to maintain the ability to and recognize and kill tumor cells. We study how T and NK cells interact with cells within the tumor microenvironment and exploit cellular and molecular mechanisms of tumor-induced immunosuppression in order to develop improved immunotherapy regimens in patients with cancer. In these studies, we use different tumor models including renal cell carcinoma, thyroid cancer, neuroblastoma, melanoma, breast cancer, and lung cancer.

Group members

Andreas Lundqvist, Group leader
Veronika Kremer, PhD student
Kristina Witt, PhD student
Maria Wolodarski, PhD student
Ziqing Chen, PhD student
Shi Yong Neo, PhD student
Lisa Liu, Post-doc
Ying Yang, associated
Marie Murray, associated

Alumni

Erik Wennerberg, Weill Cornell Medicine, New York

Dhifaf Sarhan, University of Minnesota and Karolinska Institutet

Selected publications

Genetic engineering of human NK cells to express CXCR2 improves migration to renal cell carcinoma.
Kremer V, Ligtenberg M, Zendehdel R, Seitz C, Duivenvoorden A, Wennerberg E, et al
J Immunother Cancer 2017 09;5(1):73

Zoledronic acid inhibits NFAT and IL-2 signaling pathways in regulatory T cells and diminishes their suppressive function in patients with metastatic cancer.
Sarhan D, Leijonhufvud C, Murray S, Witt K, Seitz C, Wallerius M, et al
Oncoimmunology 2017 ;6(8):e1338238

IL-15 activates mTOR and primes stress-activated gene expression leading to prolonged antitumor capacity of NK cells.
Mao Y, van Hoef V, Zhang X, Wennerberg E, Lorent J, Witt K, et al
Blood 2016 09;128(11):1475-89

Dendritic cell regulation of NK-cell responses involves lymphotoxin-α, IL-12, and TGF-β.
Sarhan D, Palma M, Mao Y, Adamson L, Kiessling R, Mellstedt H, et al
Eur. J. Immunol. 2015 Jun;45(6):1783-93

CXCL10-induced migration of adoptively transferred human natural killer cells toward solid tumors causes regression of tumor growth in vivo.
Wennerberg E, Kremer V, Childs R, Lundqvist A
Cancer Immunol. Immunother. 2015 Feb;64(2):225-35

Human anaplastic thyroid carcinoma cells are sensitive to NK cell-mediated lysis via ULBP2/5/6 and chemoattract NK cells.
Wennerberg E, Pfefferle A, Ekblad L, Yoshimoto Y, Kremer V, Kaminskyy V, et al
Clin. Cancer Res. 2014 Nov;20(22):5733-44

Inhibition of tumor-derived prostaglandin-e2 blocks the induction of myeloid-derived suppressor cells and recovers natural killer cell activity.
Mao Y, Sarhan D, Steven A, Seliger B, Kiessling R, Lundqvist A
Clin. Cancer Res. 2014 Aug;20(15):4096-106

A novel inhibitor of proteasome deubiquitinating activity renders tumor cells sensitive to TRAIL-mediated apoptosis by natural killer cells and T cells.
Sarhan D, Wennerberg E, D'Arcy P, Gurajada D, Linder S, Lundqvist A
Cancer Immunol. Immunother. 2013 Aug;62(8):1359-68

Doxorubicin sensitizes human tumor cells to NK cell- and T-cell-mediated killing by augmented TRAIL receptor signaling.
Wennerberg E, Sarhan D, Carlsten M, Kaminskyy V, D'Arcy P, Zhivotovsky B, et al
Int. J. Cancer 2013 Oct;133(7):1643-52

Activated monocytes augment TRAIL-mediated cytotoxicity by human NK cells through release of IFN-γ.
Sarhan D, D'Arcy P, Wennerberg E, Lidén M, Hu J, Winqvist O, et al
Eur. J. Immunol. 2013 Jan;43(1):249-57

List of all publications.

Funding

  • Swedish Research Council
  • Swedish Cancer Society
  • European Research Council
  • Karolinska Institutet
  • Jeanssons Stiftelse
  • Åke Wiberg Foundation
  • Magnus Bergvall Foundation
  • Fredrik och Ingrid Thurings Foundation
  • Clas Groschinskys Foundation
  • Swedish Society of Medicine
  • Wenner-Gren Foundation
  • The American Thyroid Association
  • Vinnova
Immuno TherapyImmunology