A5023554856- Immune Cell Function and Interaction
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Acute Myeloid Leukemia Research
- Cancer Immunotherapy and Biomarkers
- Chronic Myeloid Leukemia Treatments
- Lymphoma Diagnosis and Treatment
- Immune cells in cancer
- Cancer Genomics and Diagnostics
- Eosinophilic Disorders and Syndromes
- Radiomics and Machine Learning in Medical Imaging
- Chronic Lymphocytic Leukemia Research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Digital Imaging for Blood Diseases
- Hematopoietic Stem Cell Transplantation
- Hematological disorders and diagnostics
- Monoclonal and Polyclonal Antibodies Research
- AI in cancer detection
- Renal cell carcinoma treatment
- Protein Degradation and Inhibitors
- Acute Lymphoblastic Leukemia research
- Single-cell and spatial transcriptomics
- Cell Image Analysis Techniques
- Diversity and Career in Medicine
- T-cell and B-cell Immunology
University of Helsinki
2016-2024
Helsinki University Hospital
2016-2024
Baylor College of Medicine
2024
Helsinki Art Museum
2022
Finland University
2019
Institute for Molecular Medicine Finland
2016
Recent studies suggest that a proportion of chronic myeloid leukemia (CML) patients in deep molecular remission can discontinue the tyrosine kinase inhibitor (TKI) treatment without disease relapse. In this multi-center, prospective clinical trial (EURO-SKI, NCT01596114) we analyzed function and phenotype T NK cells their relation to successful TKI cessation. Lymphocyte subclasses were measured from 100 imatinib-treated at baseline 1 month after discontinuation, functional characterization...
Abstract We generated ex vivo drug-response and multiomics profiling data for a prospective series of 252 samples from 186 patients with acute myeloid leukemia (AML). A functional precision medicine tumor board (FPMTB) integrated clinical, molecular, application in clinical treatment decisions. Actionable drugs were found 97% AML, the recommendations clinically implemented 37 relapsed or refractory patients. report 59% objective response rate individually tailored therapies, including 13...
BackgroundRelatlimab plus nivolumab (anti-lymphocyte-activation gene 3 anti-programmed death 1 [anti-LAG-3+anti-PD-1]) has been approved by the FDA as a first-line therapy for stage III/IV melanoma, but its detailed effect on immune system is unknown.MethodsWe evaluated blood samples from 40 immunotherapy-naive or prior immunotherapy-refractory patients with metastatic melanoma treated anti-LAG-3+anti-PD-1 in phase I trial using single-cell RNA and T cell receptor sequencing...
Tumor microenvironment (TME) and limited immune surveillance play important roles in lymphoma pathogenesis. Here, we aimed to characterize immunological profiles of diffuse large B-cell (DLBCL), predict the outcome response immunochemotherapy. We profiled expression 730 immune-related genes tumor tissues 81 patients with DLBCL utilizing Nanostring platform, used multiplex immunohistochemistry T-cell phenotypes, including cytotoxic T-cells (CD8, Granzyme B, OX40, Ki67), checkpoint (CD3, CD4,...
Increasing evidence suggests that the immune system affects prognosis of chronic myeloid leukemia (CML), but detailed immunological composition bone marrow (BM) microenvironment is unknown. We aimed to characterize landscape CML BM and predict current treatment goal tyrosine kinase inhibitor (TKI) therapy, molecular remission 4.0 (MR4.0). Using multiplex immunohistochemistry (mIHC) automated image analysis, we studied tissues patients (n = 56) controls 14) with a total 30 immunophenotype...
Primary testicular lymphoma is a rare and aggressive lymphoid malignancy, most often representing diffuse large B-cell histologically. Tumor-associated macrophages tumor-infiltrating lymphocytes have been associated with survival in lymphoma, but their prognostic impact primary unknown. Here, we aimed to identify macrophages, immunophenotypes association lymphocytes, translate the findings into of patients lymphoma. We collected clinical data tumor tissue from 74 patients, used multiplex...
Felty syndrome is a rare disease defined by neutropenia, splenomegaly, and rheumatoid arthritis. Sometimes the differential diagnosis between large granular lymphocyte leukemia problematic. Recently, somatic STAT3 STAT5B mutations were discovered in 30–40% of patients with leukemia. Herein, we aimed to study whether these can also be detected syndrome, which would imply existence common pathogenic mechanism two entities. We collected samples clinical information from 14 who monitored at...
As novel immunological treatments are gaining a foothold in the treatment of acute lymphoblastic leukemia (ALL), it is elemental to examine ALL immunobiology more detail. We used multiplexed immunohistochemistry (mIHC) study immune contexture adult precursor B cell bone marrow (BM). In addition, we developed multivariate risk prediction model that stratified poor survival group based on clinical parameters and mIHC data. analyzed BM biopsy samples patients (n = 52) healthy controls 14) using...
Abstract The immunologic microenvironment in various solid tumors is aberrant and correlates with clinical survival. Here, we present a comprehensive analysis of the immune environment acute myeloid leukemia (AML) bone marrow (BM) at diagnosis. We compared landscape formalin-fixed paraffin-embedded BM trephine samples from AML (n = 69), chronic (CML; n 56), B-cell lymphoblastic (B-ALL) patients 52) diagnosis to controls 12) 30 immunophenotype markers using multiplex immunohistochemistry...
Abstract The prevalence and functional impact of somatic mutations in nonleukemic T cells is not well characterized, although clonal T-cell expansions are common. In immune-mediated aplastic anemia (AA), cytotoxic shown to participate disease pathogenesis. We investigated the mutation profiles AA by a custom panel 2533 genes. sequenced CD4+ CD8+ 24 patients compared results 20 healthy controls whole-exome sequencing 37 with AA. Somatic variants were common both but enriched patients’ cells,...
In myelodysplastic syndrome (MDS) and myeloproliferative neoplasm (MPN), bone marrow (BM) histopathology is assessed to identify dysplastic cellular morphology, cellularity, blast excess. Yet, other morphologic findings may elude the human eye. We used convolutional neural networks extract features from 236 MDS, 87 MDS/MPN, 11 control BM biopsies. These predicted genetic cytogenetic aberrations, prognosis, age, gender in multivariate regression models. Highest prediction accuracy was found...
Cancer-associated fibroblasts (CAFs) are molecularly heterogeneous mesenchymal cells that interact with malignant and immune confer anti- protumorigenic functions. Prior in situ profiling studies of human CAFs have largely relied on scoring single markers, thus presenting a limited view their molecular complexity. Our objective was to study the complex spatial tumor microenvironment non-small cell lung cancer (NSCLC) multiple CAF biomarkers, identify novel subsets, explore associations...
Renal cell carcinoma (RCC) is considered as an immunogenic cancer. Because not all patients respond to current immunotherapies, we aimed investigate the immunological heterogeneity of RCC tumors. We analyzedthe immunophenotype circulating, tumor, and matching adjacent healthy kidney immune cells from 52 nephrectomy with multi-parameter flow cytometry. Additionally, studied transcriptomic mutation profiles 20 clear (ccRCC) tumors bulk RNA sequencing a customized pan-cancer gene panel. The...
Primary testicular lymphoma is a rare lymphoid malignancy, most often, histologically, representing diffuse large B-cell lymphoma. The tumor microenvironment and limited immune surveillance have major impact on pathogenesis survival, but the primary unknown. Here, purpose of study was to characterize in lymphoma, associate findings with outcome. We profiled expression 730 response genes 60 lymphomas utilizing Nanostring platform, used multiplex immunohistochemistry cell phenotypes tissue....
While the abundance and phenotype of tumor-infiltrating lymphocytes are linked with clinical survival, their spatial coordination its significance remain unclear. Here, we investigated immune profile intratumoral peritumoral tissue clear cell renal carcinoma patients (n = 64). We trained a classifier to detect from hematoxylin eosin stained slides. Using unsupervised classification, were further classified into cold, hot excluded topographies reflecting lymphocyte localization. The...
Abstract Purpose: Tumor-infiltrating immune cells have prognostic significance and are attractive therapeutic targets. Yet, the clinical of their spatial organization phenotype in diffuse large B-cell lymphoma (DLBCL) is unclear. Experimental Design: We characterized T cells, macrophages, interactions by multiplex IHC (mIHC) 178 patients with DLBCL correlated data patient demographics survival. validated findings on gene expression from two external cohorts comprising 633 patients. Results:...
Treating cartilage injuries and degenerations represents an open surgical challenge. The recent advances in cell therapies have raised the need for a potent off-the-shelf source. Intra-articular injections of TGF-β transduced polydactyly chondrocytes been proposed as chronic osteoarthritis treatment but despite promising results, use gene therapy still raises safety concerns. In this study, we characterized infant, during vitro expansion chondrogenic re-differentiation. Polydactyly steady...
Purpose: Dasatinib is a short-acting dual ABL/SRC family tyrosine kinase inhibitor (TKI), which frequently used to treat chronic myeloid leukemia. Although very effective, patients taking dasatinib often display severe adverse effects, including pleural effusions and increased risk of bleeding primarily in the gastrointestinal tract. The actual causes these side effects are currently undetermined. We hypothesize that endothelial cells (ECs) line inner walls blood vessels control traffic...
Tumor microenvironment and immune escape affect pathogenesis survival in classical Hodgkin lymphoma (cHL). While tumor-associated macrophage (TAM) content has been associated with poor outcomes, macrophage-derived determinants clinical impact have remained undefined. Here, we used multiplex immunohistochemistry digital image analysis to characterize TAM immunophenotypes regard expression of checkpoint molecules programmed cell death ligand 1 (PD-L1) indoleamine 2,3-dioxygenase (IDO-1) from...
Abstract Treatment responses of patients with acute myeloid leukemia (AML) are known to be heterogeneous, posing challenges for risk scoring and treatment stratification. In this retrospective multi-cohort study, we investigated whether combining pyroptosis- immune-related genes improves prognostic classification AML patients. Using a robust gene pairing approach, which effectively eliminates batch effects across heterogeneous patient cohorts transcriptomic data, developed an immunity...