Research

The overarching objective of the current research in the Hagerling lag is to determine whether the distant metastatic site itself must be considered in treatment and drug development. To address this, we apply spatial multiomics and patient-derived xenograft (PDX) models to study both adult and pediatric metastases, aiming to resolve whether metastasis site–specific tumor cell properties and microenvironmental cues hide therapeutic targets.

Patterns of metastatic spread vary between cancer types, a clinical observation that strongly suggests metastasis formation depends on organ-specific intrinsic or acquired traits of tumor cells, as well as contributions from non-malignant accessory cells—such as immune and stromal cells—within the microenvironment. Based on this, we hypothesize that (i) organ-specific capabilities hide cellular vulnerabilities that could be targeted therapeutically, and, (ii) curative strategies for metastatic cancer will require treatments tailored to the metastatic site.

The overarching aim of our research program is to identify organ-specific therapeutic targets and prognostic biomarkers in metastasis. The research is structured into two complementary projects:

1. The Non-Random Metastatic Behavior of Neuroblastoma Reveals Therapeutic Opportunities
2. Spatial Multiomics to Decode and Target the Non-Random Metastatic Behavior of Common Adult Malignancies

Selected publications

• Christensson G, Bocci M, Kazi JU, Lanzing G, Pietras K, Gonzalez H, and Hagerling C ****Spatial multiomics reveal intratumoral immune heterogeneity with distinct cytokine networks in lung cancer brain metastases.  Cancer Res Commun. 2024 Nov 1;4(11):2888-2902.
• Valind A, Bronte Verhoeven M, Enoksson J, Karlsson J, Christensson G, Mañas A, Aaltonen K, Jansson C, Bexell D, Baryawno N, Gisselsson D and Hagerling C. Macrophage infiltration promotes regrowth in MYCN-amplified neuroblastoma after chemotherapy Oncoimmunology Mar 1;12(1):2184130, 2023
• Manouk BV, Mei S, Olsen T, Gustafsson K, Valind A, Lindström A, Gisselsson Nord D, Fard S, Hagerling C†, Kharchenko P†, Kogner P†, Johnsen J†, Baryawno N†. The Immune cell atlas of human neuroblastoma Cell Reports Medicine, Jun 21;3(6):100657 2022
• Gonzalez H, Mei W, Robles I, Hagerling C, Allen B, Nanjaraj A, Verbeek T, Kalavacherla S, Gogh M, Georgiou S, Daras M, Phillips J, H. Spitzer M, Roose J and Werb Z. Cellular Architecture of Human Brain Metastases Cell, Feb 17;185(4):729-745, 2022
• Stenström J, Hedenfalk I and Hagerling C Regulatory T lymphocyte infiltration in metastatic breast cancer-an independent prognostic factor that changes with tumor progression Breast Cancer Res, Feb 18;23(1):27, 2021
• Hagerling C, Gonzalez H, Salari K, Wang CY, Maller O, Casbon A, Lin C, Gogh M, Jirström K, Weaver V, and Werb Z. Immune effector monocyte – neutrophil cooperation induced by the primary tumor prevents metastatic progression of breast cancer PNAS, Oct 116 (43), 21704-21714, 2019
• Gonzalez H, Hagerling C and Werb Z Roles of the immune system in cancer: from tumor initiation to metastatic progression Genes and Development. **2018:**32(19-20):1267-1284