Immune cell development and cancer
Our immune system is remarkable. It is composed by a network of cells, including T and B cells that work together to protect our body from infection by pathogens such as bacteria, viruses and parasites.
During an immune response to infection, B cells undergo a T cell dependent stage of development, called germinal centre (GC), essential to produce high affinity antibodies against the pathogen. However, to produce such antibodies, B cells in the GC microenvironment undergo processes of DNA mutation and recombination while rapidly dividing, and infidelity in these processes may lead to oncogenic DNA lesions. Indeed the most common types of haematological malignancies in adults, such as Hodgkin and non-Hodgkin lymphomas and multiple myeloma, originate from B cells at the GC stage or from B cells that have passed through the GC. This emphasises the importance of the maturation events within the GC microenvironment for B cell cancer development.
Using an integrative approach to immunology and cancer biology, our Laboratory aims to understand the mechanisms by which healthy GC B cells become cancerous.
- Eswaran, J; Sinclair, P; Heidenreich, O; Irving, J; Russell, LJ; Hall, A; Calado, DP; Harrison, CJ and Vormoor, J (2015)
The pre B cell receptor checkpoint in acute lymphoblastic leukaemia.
Leukemia [Epub ahead of print] PubMed abstract
- Zhang, B; Calado, DP; Wang, Z; Fröhler, S; Köchert, K; Qian, Y; Koralov, SB; Schmidt-Supprian, M; Sasaki, Y; Unitt, C; Rodig, S; Chen, W; Dalla-Favera, R; Alt, FW; Pasqualucci, L and Rajewsky, K (2015)
An oncogenic role for alternative NF-κB signaling in DLBCL revealed upon deregulated BCL6 expression.
Cell Reports 11, 715-726 PubMed abstract
- Calado, DP; Sasaki, Y; Godinho, SA; Pellerin, A; Kochert, K; Sleckman, BP; de Alborán, IM; Janz, M; Rodig, S and Rajewsky, K (2012)
The cell-cycle regulator c-Myc is essential for the formation and maintenance of germinal centers.
Nature Immunology 13, 1092-1100 PubMed abstract
- Sander, S; Calado, DP; Srinivasan, L; Köchert, K; Zhang, B; Rosolowski, M; Rodig, SJ; Holzmann, K; Stilgenbauer, S; Siebert, R; Bullinger, L and Rajewsky, K (2012)
Synergy between PI3K signaling and MYC in Burkitt lymphomagenesis.
Cancer Cell 22, 167-179 PubMed abstract
- Wesemann, DR; Magee, JM; Boboila, C; Calado, DP; Gallagher, MP; Portuguese, AJ; Manis, JP; Zhou, X; Recher, M; Rajewsky, K; Notarangelo, LD and Alt, FW (2011)
Immature B cells preferentially switch to IgE with increased direct Sμ to Sε recombination.
Journal of Experimental Medicine 208, 2733-2746 PubMed abstract
- Calado, DP; Zhang, B; Srinivasan, L; Sasaki, Y; Seagal, J; Unitt, C; Rodig, S; Kutok, J; Tarakhovsky, A; Schmidt-Supprian, M and Rajewsky, K (2010)
Constitutive canonical NF-κB activation cooperates with disruption of BLIMP1 in the pathogenesis of activated B cell-like diffuse large cell lymphoma.
Cancer Cell 18, 580-589 PubMed abstract
- Neves, P; Lampropoulou, V; Calderon-Gomez, E; Roch, T; Stervbo, U; Shen, P; Kühl, AA; Loddenkemper, C; Haury, M; Nedospasov, SA; Kaufmann, SHE; Steinhoff, U; Calado, DP and Fillatreau, S (2010)
Signaling via the MyD88 adaptor protein in B cells suppresses protective immunity during Salmonella typhimurium infection.
Immunity 33, 777-790 PubMed abstract