Maija Hollmen

Maija Hollmen
University of Turku | UTU · MediCity Research Laboratory

PhD

About

145
Publications
20,948
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3,023
Citations
Introduction
Maija Hollmén is an adjunct professor of tumour immunology, group leader and academy research fellow at the MediCity Research Laboratory, Institute of Biomedicine, University of Turku, Finland. Her research exploits a unique scavenger receptor Clever-1, expressed on a subpopulation of immunosuppressive macrophages, to alleviate tumor related inflammation and develop Clever-1 as a companion therapeutic, diagnostic, and prognostic biomarker to treat and identify patients under immunosuppression. This involves the use of in vivo tumor models and sophisticated immunological assays with cutting-edge technology and state-of-the-art imaging combined with fresh human cancer patient material.
Additional affiliations
July 2011 - June 2014
ETH Zurich
Position
  • PostDoc Position
June 2004 - March 2010
University of Turku
Position
  • PhD Student

Publications

Publications (145)
Article
Full-text available
Secondary lymphedema is a common sequel of oncologic surgery and presents a global health burden still lacking pharmacological treatment. The infiltration of the lymphedematous extremities with CD4⁺T cells influences lymphedema onset and emerges as a promising therapy target. Here, we show that the modulation of CD4⁺FOXP3⁺CD25⁺regulatory T (Treg) c...
Preprint
Full-text available
Cancer metastasis to sentinel lymph nodes (LNs) is often the first marker of potential disease progression. Although it is recognized that tumor-induced lymphangiogenesis facilitates metastasis into LNs in murine models, tumor-induced alterations in human lymphatic vessels remain obscure. We used single-cell RNA sequencing to profile lymphatic endo...
Article
Single-nuclei RNA sequencing remains a challenge for many human tissues, as incomplete removal of background signal masks cell-type-specific signals and interferes with downstream analyses. Here, we present Quality Clustering (QClus), a droplet filtering algorithm targeted toward challenging samples. QClus uses additional metrics, such as cell-type...
Article
Introduction Treatment of myelodysplastic syndrome (MDS) with primary refractory disease or relapse after frontline treatment (r/r MDS) represents a high unmet medical need. Hypomethylating (HMA) agents, including azacitidine, are used in the frontline setting for higher-risk (HR) MDS patients with response rate reported as 16%1. After HMA-failure,...
Article
NK cell therapies offer great promise in treating hematological cancers due to their “off-the-shelf” applicability and reduced toxicity. However, challenges in specificity, potency, and longevity persist compared to T cell therapies. Genetic engineering has shown promise in enhancing NK cell function, and recent research indicates that certain onco...
Article
Background Atrio-ventricular block (AVB) can often be seen in patients undergoing cardiac procedures. Nevertheless, little is known about the histopathological features of new-onset postoperative AVB prior to the clinical manifestation and its prognostic impact. Purpose This study explores the association of first-degree AVB in ECG and postoperati...
Preprint
Full-text available
Clever–1 functions as a scavenger and adhesion receptor, promoting tolerogenic activities in macrophages and subsets of endothelial cells, thereby contributing to cancer progression. High Clever–1 expression associates with resistance to immune checkpoint inhibitors and combined targeting of Clever–1 with anti–PD–1 enhances response in refractory m...
Article
Full-text available
Chronic inflammation plays a crucial role in coronary artery disease (CAD), but differences in specific cytokine profiles between acute coronary syndrome (ACS) and stable CAD remain unknown. We investigated cytokine differences between these two manifestations of CAD. The study included 308 patients with angiographically detected, hemodynamically s...
Article
Background Systemic inflammation has a critical role in the development of symptomatic coronary artery disease (CAD). Identification of inflammatory pathways may provide a platform for novel therapeutic approaches. We sought to determine whether there are differences in circulating cytokine profiles between patients with CAD and disease-free contro...
Article
Full-text available
Background Mobilization of certain immune cells may improve the ability of the immune system to combat tumor cells, but the effect of acute exercise on mobilizing immune cells has been sparsely investigated in cancer patients. Therefore, we examined how acute exercise influences circulating immune cells in breast cancer patients. Methods Nineteen...
Article
Full-text available
Tumour-associated macrophages (TAMs) sustain a tumour-supporting and immunosuppressive milieu and therefore aggravate cancer prognosis. To modify TAM behaviour and unlock their anti-tumoural potential, novel TAM-reprogramming immunotherapies are being developed at an accelerating rate. At the same time, scientific discoveries have highlighted more...
Preprint
Tumor-resident immune cells play a crucial role in eliciting anti-tumor immunity and immunomodulatory drug responses, yet these functions have been difficult to study without tractable models of tumor immune microenvironment (TIME). Patient-derived ex vivo models contain authentic resident immune cells and therefore, could provide new mechanistic i...
Article
Cardiovascular disease plays a central role in the electrical and structural remodeling of the right atrium, predisposing to arrhythmias, heart failure, and sudden death. Here, we dissect with single-nuclei RNA sequencing (snRNA-seq) and spatial transcriptomics the gene expression changes in the human ex vivo right atrial tissue and pericardial flu...
Article
Full-text available
Background Combining cytotoxic chemotherapy or novel anticancer drugs with T-cell modulators holds great promise in treating advanced cancers. However, the response varies depending on the tumor immune microenvironment (TIME). Therefore, there is a clear need for pharmacologically tractable models of the TIME to dissect its influence on mono- and c...
Article
Full-text available
Macrophage Clever-1 contributes to impaired antigen presentation and suppression of anti-tumor immunity. This first-in-human trial investigates the safety and tolerability of Clever-1 blockade with bexmarilimab in patients with treatment-refractory solid tumors and assesses preliminary anti-tumor efficacy, pharmacodynamics, and immunologic correlat...
Article
Background Clever-1 (common lymphatic endothelial and vascular endothelial receptor-1) constitutes a novel macrophage checkpoint. The receptor contributes to immune tolerance by antigen clearing and T cell inhibition. In multiple models, tumor growth is significantly reduced when Clever-1 function is inhibited. Expression of Clever-1 on bone marrow...
Article
Full-text available
Immune checkpoint inhibitors show substantially greater efficacy in inflamed tumors characterized by pre-existing T cell infiltration and interferon (IFN) signaling than in non-inflamed, “cold”, tumors, which often remain immunotherapy resistant. The cancer immunotherapy bexmarilimab, which inhibits the scavenger receptor Clever-1 to release macrop...
Conference Paper
Full-text available
Background Clever-1 is an immunosuppressive scavenger receptor expressed on tumor-associated macrophages (TAM). High levels of Clever-1 are associated with poor survival, T-cell exclusion and dysfunction, and immunotherapy resistance.¹ Bexmarilimab (FP-1305, Bex) is a novel humanized anti-Clever-1 IgG4-antibody capable of promoting an immune switch...
Article
Full-text available
Objective Patients undergoing heart surgery are at high risk of postoperative fluid accumulation due to long procedures and cardiopulmonary bypass. In the present study, we sought to investigate the prevalence of postoperative fluid accumulation and its relation to adverse events in patients undergoing cardiac surgery. Methods CAREBANK is prospect...
Preprint
Full-text available
Secondary lymphedema is a common sequel of oncologic surgery following lymphatic injury and presents a substantial global health burden for which no pharmacological treatment exists. The infiltration of the affected lymphedematous extremities with CD4⁺T-cells has been shown to influence lymphedema onset. Various approaches towards their manipulatio...
Article
Hyperferritinemia is a frequent finding in several conditions, both genetic and acquired. We previously studied eleven healthy subjects from eight different families presenting with unexplained hyperferritinemia. Their findings suggested the existence of an autosomal-recessive disorder. We carried out whole-exome sequencing to detect the genetic ca...
Preprint
Combining cytotoxic chemotherapy or novel anticancer drugs with T-cell modulators holds great promise in treating advanced cancers. However, the response varies depending on the tumor immune microenvironment (TIME). Therefore, there is a clear need for pharmacologically tractable models of the TIME to dissect its influence on mono- and combination...
Article
The potential of immunotherapies in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) remains still under investigation. Clever-1 (also known as Stabilin-1) is a multifunctional scavenger and adhesion receptor expressed by monocytes and immunosuppressive macrophages. Bexmarilimab, a Clever-1 targeting antibody, demonstrates many immun...
Article
Full-text available
The role of exercise in cancer prevention and control is increasingly recognized, and based on preclinical studies, it is hypothesized that mobilization of leukocytes plays an important role in the anti-tumor effect. Thus, we examined how 10-min acute exercise modulates immune cells in newly diagnosed breast cancer patients. Blood samples were take...
Preprint
Clever-1 expression in macrophages contributes to impaired antigen presentation and suppression of anti-tumor immunity. This first-in-human trial was designed to investigate the safety and tolerability of Clever-1 blockade in patients with treatment-refractory solid tumors and to assess preliminary anti- tumor efficacy, pharmacodynamics, and immuno...
Article
Globally, breast cancer is among the most diagnosed cancer types for women. Current and upcoming breast cancer therapies are being investigated in combination with compounds that stimulate an immune response, but whether the therapeutic agents themselves have unexpected immunomodulatory effects is often overlooked. Here, we have developed a method...
Article
Introduction: Bexmarilimab, a Clever-1 targeting humanized antibody, is a macrophage checkpoint inhibitor promoting antigen presentation and pro-inflammatory cytokine secretion. Data from the first-in-human clinical Phase I/II study (MATINS; NCT03733990) demonstrate that single agent bexmarilimab is able to ignite an interferon response with surviv...
Article
Introduction: Clever-1 is an immunosuppressive scavenger receptor expressed on tumor associated macrophages. High levels of Clever-1 are associated with poor survival, T-cell exclusion and dysfunction, and immunotherapy resistance. Bexmarilimab (FP-1305) is a novel humanized anti-Clever-1 IgG4-antibody capable of promoting an immune switch, potenti...
Article
Full-text available
Background: The use of glucocorticoids has given contradictory results for treating acute respiratory distress syndrome (ARDS). The use of intravenous Interferon beta (IFN β) for the treatment of ARDS was recently tested in a phase III ARDS trial (INTEREST), in which more than half of the patients simultaneously received glucocorticoids. Trial res...
Article
The immunosuppressive tumor microenvironment governed by tumor-associated macrophages (TAMs) remains a major obstacle to effective cancer immunotherapy. A novel humanized antibody bexmarilimab, targeting the scavenger receptor Clever-1 on TAMs, has shown clinical benefit in ~40% of patients with late-stage ER+ breast cancer (MATINS; NCT03733990). T...
Article
Full-text available
Enhancing our understanding of lymphatic anatomy from the microscopic to the anatomical scale is essential to discern how the structure and function of the lymphatic system interacts with different tissues and organs within the body and contributes to health and disease. The knowledge of molecular aspects of the lymphatic network is fundamental to...
Article
Full-text available
Background: Studies have shown that acute exercise can mobilize several leukocyte subpopulations in healthy individuals. Our aim was to investigate whether a 10-min acute exercise has an effect on immune cell proportions in lymphoma patients. Methods: This study included seven lymphoma patients referred to curative oncologic therapy. Three had Hodg...
Article
Full-text available
Lipedema is a chronic and progressive adipose tissue disorder, characterized by the painful and disproportionate increase of the subcutaneous fat in the lower and/or upper extremities. While distinct immune cell infiltration is a known hallmark of the disease, its role in the onset and development of lipedema remains unclear. To analyze the macroph...
Article
The lack of T-cell infiltrates is a major obstacle to effective immunotherapy in cancer. Conversely, the formation of tumor-associated tertiary-lymphoid-like structures (TA-TLS), which are the local site of humoral and cellular immune responses against cancers, are associated with good prognosis and have recently been detected in Immune Checkpoint...
Preprint
Serum ferritin measurement is a routine laboratory test to indirectly evaluate body iron content. However, many additional factors may elevate serum ferritin levels disproportionally to iron stores. Hyperferritinemia is a frequent finding in several conditions, both genetic and acquired. Despite the long history of clinical use, fundamental aspects...
Article
The lack of T cell infiltrates is a major obstacle to effective immunotherapy in cancer. Conversely, the formation of tumor-associated tertiary-lymphoid-like structures (TA-TLLSs), which are the local site of humoral and cellular immune responses against cancers, is associated with good prognosis, and they have recently been detected in immune chec...
Article
Full-text available
Bexmarilimab is a new humanized monoclonal antibody against common lymphatic endothelial and vascular endothelial receptor-1 (CLEVER-1), and is in clinical trials for macrophage-guided cancer immunotherapy. In addition to cancer, CLEVER-1 is also associated with fibrosis. To facilitate prospective human PET studies, we preclinically evaluated 89Zr-...
Preprint
Full-text available
Single nuclei RNA sequencing (snRNA-seq) is widely used to study tissues and diseases. However, the technique remains challenging, as cytoplasmic RNA often contaminates nuclei-containing droplets and may even complicate the removal of empty droplets. Incomplete removal of contaminated background signal masks cell type-specific signal and interferes...
Article
Full-text available
Papillary thyroid carcinoma (PTC) is the most frequent histological subtype of thyroid cancers (TC), and BRAFV600E genetic alteration is found in 60% of this endocrine cancer. This oncogene is associated with poor prognosis, resistance to radioiodine therapy, and tumor progression. Histological follow-up by anatomo-pathologists revealed that two-th...
Article
Full-text available
Renal cell carcinoma (RCC) accounts for 90% of all renal cancers and is considered highly immunogenic. Although many studies have reported the circulating peripheral cytokine profiles, the signatures between the tumor tissue and matching healthy adjacent renal tissue counterparts have not been explored. We aimed to comprehensively investigate the c...
Article
Full-text available
Purpose Common Lymphatic Endothelial and Vascular Endothelial Receptor 1 (Clever-1) is expressed by a subset of immunosuppressive macrophages and targeting the receptor with therapeutic antibodies has been shown to activate T-cell-mediated anti-cancer immunity. The aim of this research was to study Clever-1 expression in breast cancer. Specifically...
Preprint
Papillary thyroid carcinoma (PTC) is the most frequent histological subtype of thyroid cancers (TC), and BRAF V600E genetic alteration is found in 60% of this endocrine cancer. This oncogene is associated with poor prognosis, resistance to radioiodine therapy and tumor progression. Histological follow-up by anatomo-pathologists reveals that 2/3 of...
Article
2645 Background: Clever-1 is an immunosuppressive scavenger receptor expressed on tumor associated macrophages. High levels of Clever-1 are associated with poor survival and immunotherapy resistance. Bexmarilimab (FP-1305) is a novel humanized anti-CLEVER-1 IgG4-antibody capable of inducing a phenotypic M2 to M1 immune switch of tumor-associated ma...
Article
Full-text available
Common lymphatic endothelial and vascular endothelial receptor-1 (Clever-1) is a multifunctional type-1 transmembrane protein that plays an important role in immunosuppression against tumors. Clever-1 is highly expressed in a subset of human tumor-associated macrophages and associated with poor survival. In mice, Clever-1 supports tumor growth and...
Preprint
Full-text available
The use of glucocorticoids has given contradictory results for treating acute respiratory distress syndrome (ARDS). Here we report a novel disease association of a SNP rs9984273, which is situated in the interferon alpha/beta receptor (IFNAR2) gene in an area corresponding to a binding motif of the glucocorticoid receptor (GR). The minor allele of...
Preprint
Full-text available
Purpose Renal cell carcinoma (RCC) accounts for 90% of all renal cancers and is considered highly immunogenic. Although many studies have reported the circulating peripheral cytokine profiles, the signatures between the tumor tissue and matching healthy adjacent renal tissue counterparts have not been explored. We aimed to comprehensively investiga...
Preprint
Full-text available
Purpose Renal cell carcinoma (RCC) accounts for 90% of all renal cancers and is considered highly immunogenic. Although many studies have reported the circulating peripheral cytokine profiles, the signatures between the tumor tissue and matching healthy adjacent renal tissue counterparts have not been explored. We aimed to comprehensively investiga...
Article
Full-text available
Although the development of hematopoietic stem cells (HSC) has been studied in great detail, their heterogeneity and relationships to different cell lineages remain incompletely understood. Moreover, the role of Vascular Adhesion Protein-1 in bone marrow hematopoiesis has remained unknown. Here we show that VAP-1, an adhesin and a primary amine oxi...
Article
Full-text available
Melanocortin receptor 1 (MC1-R) is expressed in leukocytes, where it mediates anti-inflammatory actions. We have previously observed that global deficiency of MC1-R signaling perturbs cholesterol homeostasis, increases arterial leukocyte accumulation and accelerates atherosclerosis in apolipoprotein E knockout (Apoe-/-) mice. Since various cell typ...
Article
Background: Atrial cardiomyopathy (ACM) is characterized by multiple histopathological features but the entity lacks systematic validation. Objectives: We sought to correlate atrial histopathology with clinical characteristics of patients with ACM and AF and outcomes following cardiac surgery. Methods: The pathological findings of the atrial myocar...
Article
Full-text available
Patients undergoing cardiac surgery develop a marked postoperative systemic inflammatory response. Blood transfusion may contribute to disruption of homeostasis in these patients. We sought to evaluate the impact of blood transfusion on serum interleukin-6 (IL-6), hypoxia induced factor-1 alpha (HIF-1α) levels as well as adverse outcomes in patient...
Preprint
Full-text available
Ischemic heart disease is globally the leading cause of death. It plays a central role in the electrical and structural remodeling of the right atrium, predisposing to arrhythmias, heart failure, and sudden death. Here, we provide the first dissection of the gene expression changes in the live right atrial tissue, using single-nuclei RNA-seq and sp...
Article
Full-text available
Purpose: Macrophages are critical in driving an immunosuppressive tumor microenvironment that counteracts the efficacy of T-cell-targeting therapies. Thus, agents able to reprogram macrophages towards a proinflammatory state hold promise as novel immunotherapies for solid cancers. Inhibition of a macrophage scavenger receptor Clever-1 has shown be...
Article
Background: To investigate the potential of intravenously administered porcine recombinant interferon-β1a (IFN-β1a) for myocardial protection during acute ischemia-reperfusion (IR) injury in an experimental animal model. Methods: Twenty-two piglets (mean ± standard deviation, 26.7 ± 1.65 kg) were assigned to either the IFN group (n = 12) or the...
Article
Full-text available
Background: Synovial fluid bacterial culture is the cornerstone of confirmation or exclusion of periprosthetic joint infection (PJI). The aim of this study was to assess synovial fluid and serum biomarker patterns of patients with total joint arthroplasty (TJA), and the association of these patterns with PJI. Methods: Synovial fluid and serum sa...
Article
Full-text available
Lipedema is an adipose tissue disorder characterized by the disproportionate increase of subcutaneous fat tissue in the lower and/or upper extremities. The underlying pathomechanism remains unclear and no molecular biomarkers to distinguish the disease exist, leading to a large number of undiagnosed and misdiagnosed patients. To unravel the distinc...
Article
Full-text available
Clever-1 also known as Stabilin-1 and FEEL-1 is a scavenger molecule expressed on a subpopulation of anti-inflammatory macrophages and lymphatic endothelial cells (LECs). However, its role in regulating dendritic cell (DC) trafficking and subsequent effects on immunity have remained unexplored. In this study, we demonstrate that DC trafficking from...
Article
Full-text available
Toll-like receptor 5 ligand, flagellin, and vascular adhesion protein 1 (VAP-1) are involved in non-alcoholic fatty liver disease. This study aimed to determine whether VAP-1 mediates flagellin-induced hepatic fat accumulation. The effects of flagellin on adipocyte VAP-1 expression were first studied in vitro. Then, flagellin (100 ng/mouse) or sali...
Article
Genome-wide association studies have uncovered over 200 genetic loci underlying coronary artery disease (CAD), providing great hope for a deeper understanding of the causal mechanisms leading to this disease. However, in order to understand CAD at the molecular level, it is necessary to uncover cell-type-specific circuits and to use these circuits...
Preprint
Macrophages are critical in driving an immunosuppressive tumor microenvironment that counteracts the efficacy of T-cell targeting therapies. Thus, agents that can reprogram macrophages towards a proinflammatory state hold promise as novel immunotherapies for solid cancers. Here, we report that immunotherapeutic targeting of the macrophage scavenger...
Article
Background Systemic inflammation has a critical role in the development of coronary artery disease (CAD). Identification of inflammatory pathways may provide a platform for novel therapeutic approaches. Purpose We sought to determine whether there are differences in circulating cytokine profiles between patients with CAD and disease-free controls....