Group Per-Ola Andersson

Research summary

Despite advances in both treatment and genetic classification of diffuse large B-cell lymphoma (DLBCL), around 25% of patients still die from their disease. DLBCL is a heterogeneous tumor where both the malignant clone and the tumor microenvironment contribute to the variable clinical picture. However, the complexity can probably not only be explained by genetic changes, and it is also difficult to predict whether such changes really affect protein expression and thus the phenotype of the tumor cell.

By parallel studies on global protein expression, RNA-sequencing and digital image analysis of immunohistochemical staining in tumor tissue from DLBCL patients, we have found that overexpression of interferon-stimulated genes/proteins (especially belonging to the PYHIN group), appears to affect both prognosis and response to treatment. After performing further in vitro studies in DLBCL cell lines, our data also indicate a functional role.

Interferon-stimulated genes (ISGs) play an important role primarily in antiviral immunity, but in recent years it has become increasingly evident that they can also affect immunosuppressive mechanisms in various forms of cancer and then induce both tumor progression and treatment resistance. Their significance in DLBCL is so far unknown.

The main purpose of the project is to test the hypothesis if interferon-stimulated proteins, primarily from the PYHIN group, influence treatment resistance in DLBCL and if they could be of therapeutic potential.

Research tools and resources

Based on our previous findings in tumor tissue from DLBCL patients, we use DLBCL cell lines of different sensitivity to the CHOP-regimen and investigate the functional role of different interferon-stimulated genes/proteins. 

We use shRNA-based downregulation, co-culturing with immunochemotherapeutic agents, standard techniques such as PCR, western blot, cell proliferation/apoptosis assays with flow cytometry. We are also aiming to develop DLBCL mouse models and therapeutic ISG-protein degraders. 

Current group members

P-O Andersson, adjunct professor in hematology and senior hematology consultant
Samskruthi Saresh, Research assistant
Ebba Stål, Research assistant

Selected publications

1. Temporal trends in relative survival of diffuse large B-cell lymphoma in Sweden and Denmark in the era of targeted and cellular therapies.
   Harrysson S, Eloranta S, Antonilli S, Runason Simonsen M, Sonnevi K, Brown P, Wahlin BE, Andersson PO, Jørgensen JM, Jerkeman M, Poulsen CB, Enblad G, El-Galaly TC, Smedby KE. Br J Haematol. 2025 Jun;206(6):1834-1839.
    
2. Outcomes for patients with secondary CNS involvement in relapsed/refractory diffuse large B-cell lymphoma and estimation of eligibility for CAR T-cell therapy.
   Harrysson S, Eloranta S, Ekberg S, Enblad G, Andersson PO, Sonnevi K, Ljungqvist M, Sander B, Jerkeman M, Smedby KE. Leuk Lymphoma. 2024 Apr;65(4):534-537.
    
3. Bone marrow expression of CD68/CD163 macrophages, IL-17 and FOXP3 cells in aplastic anemia and their relation to prognosis.
   Vaht K, Brenner J, Ednersson SB, Ljungman P, Brune M, Andersson PO. Eur J Haematol. 2023 Mar;110(3):313-321.
    
4. Proteomic analysis in diffuse large B-cell lymphoma identifies dysregulated tumor microenvironment proteins in non-GCB/ABC subtype patients.
   Bram Ednersson S, Stern M, Fagman H, Nilsson-Ehle H, Hasselblom S, Thorsell A, Andersson PO. Leuk Lymphoma. 2021 Oct;62(10):2360-2373.
    
5. TBLR1 and CREBBP as potential novel prognostic immunohistochemical biomarkers in diffuse large B-cell lymphoma.
   Ednersson SB, Stern M, Fagman H, Nilsson-Ehle H, Hasselblom S, Andersson PO. Leuk Lymphoma. 2020 Nov;61(11):2595-2604.
    
6. Expression of ribosomal and actin network proteins and immunochemotherapy resistance in diffuse large B cell lymphoma patients.
   Bram Ednersson S, Stenson M, Stern M, Enblad G, Fagman H, Nilsson-Ehle H, Hasselblom S, Andersson PO. Br J Haematol. 2018 Jun;181(6):770-781.
    
7. Serum nuclear magnetic resonance-based metabolomics and outcome in diffuse large B-cell lymphoma patients - a pilot study.
   Stenson M, Pedersen A, Hasselblom S, Nilsson-Ehle H, Karlsson BG, Pinto R, Andersson PO. Leuk Lymphoma. 2016 Aug;57(8):1814-22.

More group Per-Ola Andersson publications on PubMed