Carina Strell
The Early Breast Cancer Research Group.
The Strell group
Carina Strell holds a diploma in biochemistry (2004) and a PhD in tumor biology (2009) from the Witten/Herdecke University in Germany. She performed her postdoctoral studies in the group of Professor Arne Östman at the Karolinska Institute, where she started working on DCIS (2010–2016). Thereafter, Strell worked as a senior researcher in Professor Mats Nilsson’s lab at the Science for Life Laboratory in Stockholm, focusing on in situ sequencing to spatially study gene expression patterns in breast cancer. In 2019, she moved to Uppsala University, where she qualified as associate professor in experimental pathology in 2020 and was appointed independent PI in 2023 (continued affiliation). Supported by a Starting Grant from the Trond Mohn Research Foundation (TMF) in 2022, Strell became a CCBIO-affiliated principal investigator and now holds a researcher position at the University of Bergen (UiB).
Brief group presentation and history
The Early Breast Cancer Group was established in 2022, after Carina Strell received a TMF Starting Grant and became a CCBIO-associated principal investigator. The group comprises one researcher (Lars Muhl), one postdoc (Anna Gorbunova) and one PhD student (Ghazal Toussi) at the UiB site, and one researcher (Aglaia Schiza), two PhD students (Viktoria Thurfjell, Amanda Lindberg) and one lab manager (Neda Hekmati) at the Uppsala site.
Research focus
The research in Strell’s group focuses on the biology of breast ductal carcinoma in situ (DCIS), with the overall ambition to comprehensively elucidate the underlying regulatory signaling mechanisms of early breast cancer evolution towards clinical disease progression and therapy response. Special emphasis is placed on understanding the interplay between genetic alterations and the tumor microenvironment by using state-of-the-art spatial mapping techniques for tissue analysis. Moreover, Strell’s team extend their investigation beyond biological aspects, aiming to uncover new therapeutic possibilities and develop clinically relevant treatment stratification models tailored for women with early-stage breast cancer.
Subprojects
1.EvoMaps — understanding the interplay of genetic alterations and the tumor microenvironment in DCIS
2. Study the impact of the DCIS immune architecture on disease progression
3. ImSignal — mapping active immune cell signaling
See the main web pages for the Early Breast Cancer Research Group here.
Translational, clinical, and societal importance
- Stromal PDGFRb as a response predictive biomarker for radiotherapy benefit in DCIS and early breast cancer; currently undergoing independent validation studies in a collaboration with a US based breast cancer diagnostic company.
- PD1-PDL1 interaction as a response predictive biomarker for efficacy of PD1/PDL1 targeting immune checkpoint inhibition in NSCLC; currently the group performs independent validation studies and test the predictive capacity in other solid cancers treated with immunotherapy.
- Myxoid stroma matrix as a marker for high risk of invasive progression of DCIS; the group is looking into potential independent validation cohorts.
Future perspectives
The research team will prioritize the adaptation of their established spatial tissue profiling techniques to the Hyperion Imaging System. This will complement the ongoing spatial proteomics efforts at CCBIO with approaches for spatial genomics and signaling pathway mapping. The group will also seek contacts with CCBIO bioinformaticians and big data specialists to facilitate the integration of multiple layers with different spatial omics data into current bioinformatical analysis pipelines for tissue profiling.
Results from the CoE period 2013-2024
Most important results
EvoMaps
Genetic alterations required for invasion were already detected at the in situ stage of breast cancer. This major discovery prompts the hypothesis that cancer cell invasion into surrounding tissues is largely influenced by characteristics of the tumor microenvironment.
b) In DCIS cases, HER2 amplification represents 30%, correlating with heightened T-cell infiltration and a poor prognosis. In invasive breast cancer, only 15% of cases are HER2 positive.
DCIS immune architecture
a) In contrast to findings in invasive breast cancer, the group found that high TILs level in DCIS are associated with an increased recurrence risk. This study was addressed by a Commentary in Eur J Cancer, “The Art of Thinking Counterintuitive”, highlighting that this study shows that some of the established dogmas within invasive cancers may not apply for early cancer stages. Moreover, the clinical significance of this study lies in the ability of TILs scoring to refine the definition of low-risk DCIS. Integration of TILs scoring into diagnostic routines,
as conducted on H/E sections, offers a straightforward
approach.
b) In DCIS, the presence of a softer extracellular matrix (myxoid matrix) along with TILs directly interacting with lesions is specifically linked to invasive recurrences.
ImSignal
a) In NSCLC, the interaction between PD1-PDL1, evaluated through second-generation proximity ligation assay, emerges as a new, superior predictive biomarker for immunotherapy benefit compared to the current standard of PDL1 protein assessment by IHC.
b) Furthermore, the group can map PDL2-PD1 interactions in tissue samples and investigate their role as a potential resistance mechanism. An adaptation of the PLA to the Hyperion Imaging System is ongoing.
Most important papers
1. Strell C et al. Use of beta-blockers in patients with ductal carcinoma in situ and risk of invasive breast cancer recurrence: a Swedish retrospective cohort study. Breast Cancer Res Treat 2024. PMID: 38763971.
2. Lomakin A et al. Spatial genomics maps the structure, nature and evolution of cancer clones. Nature 2022. PMID: 36352222.
3. Schiza A et al. Tumour-infiltrating lymphocytes add prognostic information for patients with low-risk DCIS: findings from the SweDCIS randomised radiotherapy trial. Eur J Cancer 2022. PMID: 35236568.
4. Strell C et al. High PDGFRb Expression Predicts Resistance to Radiotherapy in DCIS within the SweDCIS Randomized Trial. Clin Cancer Res 2021. PMID: 33952629.
Other important outputs and achievements
Findings from the ImSignal project were presented at the Keystone Symposium on Cancer Immunotherapy and the AACR Annual Meeting 2024. Amanda Lindberg received a travel grant for the Keystone symposium; PhD student Viktoria Thurfjell received a clinical PhD fellowship from the Swedish Bröstcancerförbundet.
CCBIO significance
"CCBIO offers the ideal framework for tissue-based studies with a focus on biomarker discovery and the identification of new cancer treatment targets. It inspires new collaborations and exchanges between researchers with complementary backgrounds and experiences."