ORCID Profile
0000-0002-1380-9939
Current Organisation
University of Helsinki
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: American Association for Cancer Research (AACR)
Date: 12-2016
DOI: 10.1158/2159-8290.CD-16-0577
Abstract: Immunotherapy has recently entered a renaissance phase with the approval of multiple agents for the treatment of cancer. Immunotherapy stands ready to join traditional modalities, including surgery, chemotherapy, radiation, and hormone therapy, as a pillar of cancer treatment. Although immunotherapy has begun to have success in advanced cancer treatment, its scheduling and efficacy with surgery to treat earlier stages of cancer and prevent distant metastases have not been systematically examined. Here, we have used two models of spontaneously metastatic breast cancers in mice to illustrate the significantly greater therapeutic power of neoadjuvant, compared with adjuvant, immunotherapies in the context of primary tumor resection. Elevated and sustained peripheral tumor-specific immune responses underpinned the outcome, and blood s ling of tumor-specific CD8+ T cells immediately prior to and post surgery may provide a predictor of outcome. These data now provide a strong rationale to extensively test and compare neoadjuvant immunotherapy in humans. Significance: We demonstrate the significantly greater therapeutic efficacy of neoadjuvant, compared with adjuvant, immunotherapies to eradicate distant metastases following primary tumor resection. Elevated and sustained peripheral tumor-specific immune responses underpinned the outcome, and blood s ling of tumor-specific CD8+ T cells immediately prior to and post surgery may provide a predictor of outcome. Cancer Discov 6(12) 1382–99. ©2016 AACR. See related commentary by Melero et al., p. 1312. This article is highlighted in the In This Issue feature, p. 1293
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2326-6066.22544841
Abstract: Supplementary Table 3
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2326-6066.22544847.V1
Abstract: Supplementary Table 1
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2326-6066.22544844
Abstract: Supplementary Table 2
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2326-6066.22544847
Abstract: Supplementary Table 1
Publisher: Springer Science and Business Media LLC
Date: 12-2017
Publisher: Frontiers Media SA
Date: 22-05-2019
Publisher: Scientific Societies
Date: 07-2008
Abstract: Quorum sensing (QS), a population-density-sensing mechanism, controls the production of the main virulence determinants, the plant cell-wall-degrading enzymes (PCWDEs) of the soft-rot phytopathogen Erwinia carotovora subsp. carotovora. In this study, we used random transposon mutagenesis with a gusA reporter construct to identify two new QS-controlled genes encoding the regulator Hor and a plant ferredoxin-like protein, FerE. The QS control of the identified genes was executed by the QS regulators ExpR1 and ExpR2 and mediated by the global repressor RsmA. Hor was shown to contribute to bacterial virulence at least partly through its control of PCWDE production. Our results showed that FerE contributes to oxidative stress tolerance and in planta fitness of the bacteria and suggest that QS could be central to control of oxidative stress tolerance. The presence of the FerE protein appears to be rather unique in heterotrophic bacteria and suggests an acquisition of the corresponding gene from plant host by horizontal gene transfer.
Publisher: Frontiers Media SA
Date: 28-05-2019
Publisher: Future Medicine Ltd
Date: 05-2016
DOI: 10.2217/IMT.16.7
Abstract: Aim: We compared fresh and in vitro expanded human Tregs for their CTLA4 splicing isoform expression. Methods: The CD4 + CD25 + CD127 low/- phenotype was used for sorting Tregs and mRNA levels were measured with relative qRT-PCR. Results: In fresh Tregs the level of soluble CTLA4 (sCTLA4) was half of that of full-length CTLA4, whereas in expanded cells sCTLA4 level was tenfold lower. The most striking change took place early on: sCTLA4 expression decreased significantly when cells were simply kept in culture. Conclusion: In the in vitro expanded Tregs, the splicing of CTLA4 is affected. Our findings can be significant for clinical cell manufacturing. First, even minimal processing of cells may impact the functional molecules. Second, Treg expansion yields more potent CTLA4 receptor bearing cells.
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2326-6066.22544856.V1
Abstract: Supplementary Figure Legends
Publisher: Informa UK Limited
Date: 14-02-2018
Publisher: University of Queensland Library
Date: 2019
Publisher: American Society for Clinical Investigation
Date: 25-07-2019
Publisher: Springer Science and Business Media LLC
Date: 27-11-2019
DOI: 10.1186/S12905-019-0846-7
Abstract: Health inequities inhibit global development and achievement of the Sustainable Development Goals. One gendered health area, Menstrual Health & Hygiene (MHH), has received increasing attention in Low- and Middle-Income Countries as a barrier to health, wellbeing, and gender equity. Recent anecdotal evidence in Australia highlights that MHH also present challenges to High Income Countries, particularly among underrepresented populations, such as Indigenous Australian peoples, people from low socio-economic backgrounds, or communities that are remotely located. In this article, we chart the emergence of attention to MHH in the Australian context and highlight key considerations for the conduct of research with Aboriginal and Torres Strait Islander Peoples within the culturally- and gender-sensitive area of MHH. Further we draw on insights offered by a partnership between female Aboriginal and Torres Strait Islander leaders, NGO stakeholders, and non-Indigenous researchers. Through a convening (yarning circle) held in March 2018, the group identified multiple socioecological considerations for MHH research and practice, including: affordability and access to menstrual products, barriers to knowledge and culturally sensitive education, infrastructure and supply chain challenges, and the necessity of Indigenous-led research and community-driven data collection methods in addressing the sensitive topic. We draw together these insights to develop recommendations for future research, advocacy, and action in Australia.
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2326-6066.22544856
Abstract: Supplementary Figure Legends
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2326-6066.22544844.V1
Abstract: Supplementary Table 2
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2326-6066.22544850.V1
Abstract: Supplementary Figures 1-10
Publisher: American Association for Cancer Research (AACR)
Date: 24-09-2021
DOI: 10.1158/2326-6066.CIR-21-0094
Abstract: Dendritic cells (DC), the classic antigen-presenting cells of the immune system, switch from an adhesive, phagocytic phenotype in tissues, to a mature, nonadhesive phenotype that enables migration to lymph nodes to activate T cells and initiate antitumor responses. Monocyte-derived DCs are used in cancer immunotherapy, but their clinical efficacy is limited. Here, we show that cultured bone marrow–derived DCs (BM-DC) expressing dysfunctional β2-integrin adhesion receptors displayed enhanced tumor rejection capabilities in B16.OVA and B16-F10 melanoma models. This was associated with an increased CD8+ T-cell response. BM-DCs expressing dysfunctional β2-integrins or manipulated to disrupt integrin adhesion or integrin/actin/nuclear linkages displayed spontaneous maturation in ex vivo cultures (increased costimulatory marker expression, IL12 production, and 3D migration capabilities). This spontaneous maturation was associated with an altered DC epigenetic/transcriptional profile, including a global increase in chromatin accessibility and H3K4me3/H3K27me3 histone methylation. Genome-wide analyses showed that H3K4me3 methylation was increased on DC maturation genes, such as CD86, Il12, Ccr7, and Fscn1, and revealed a role for a transcription factor network involving Ikaros and RelA in the integrin-regulated phenotype of DCs. Manipulation of the integrin-regulated epigenetic landscape in wild-type ex vivo–cultured BM-DCs enhanced their functionality in tumor rejection in vivo. Thus, β2-integrin–mediated adhesion to the extracellular environment plays an important role in restricting DC maturation and antitumor responses through regulation of the cellular epigenetic and transcriptional landscape. Targeting β2-integrins could therefore be a new strategy to improve the performance of current DC-based cancer immunotherapies.
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2326-6066.C.6550764.V1
Abstract: Abstract Dendritic cells (DC), the classic antigen-presenting cells of the immune system, switch from an adhesive, phagocytic phenotype in tissues, to a mature, nonadhesive phenotype that enables migration to lymph nodes to activate T cells and initiate antitumor responses. Monocyte-derived DCs are used in cancer immunotherapy, but their clinical efficacy is limited. Here, we show that cultured bone marrow–derived DCs (BM-DC) expressing dysfunctional β2-integrin adhesion receptors displayed enhanced tumor rejection capabilities in B16.OVA and B16-F10 melanoma models. This was associated with an increased CD8 sup + /sup T-cell response. BM-DCs expressing dysfunctional β2-integrins or manipulated to disrupt integrin adhesion or integrin/actin/nuclear linkages displayed spontaneous maturation in i ex vivo /i cultures (increased costimulatory marker expression, IL12 production, and 3D migration capabilities). This spontaneous maturation was associated with an altered DC epigenetic/transcriptional profile, including a global increase in chromatin accessibility and H3K4me3/H3K27me3 histone methylation. Genome-wide analyses showed that H3K4me3 methylation was increased on DC maturation genes, such as i CD86 /i , i Il12 /i , i Ccr7 /i , and i Fscn1 /i , and revealed a role for a transcription factor network involving Ikaros and RelA in the integrin-regulated phenotype of DCs. Manipulation of the integrin-regulated epigenetic landscape in wild-type i ex vivo /i –cultured BM-DCs enhanced their functionality in tumor rejection i in vivo /i . Thus, β2-integrin–mediated adhesion to the extracellular environment plays an important role in restricting DC maturation and antitumor responses through regulation of the cellular epigenetic and transcriptional landscape. Targeting β2-integrins could therefore be a new strategy to improve the performance of current DC-based cancer immunotherapies. /
Publisher: Oxford University Press (OUP)
Date: 25-12-2019
DOI: 10.1111/CEI.13407
Abstract: T cell immunoglobulin and ITIM domain (TIGIT) is an inhibitory receptor expressed on lymphocytes that was recently propelled under the spotlight as a major emerging target in cancer immunotherapy. TIGIT interacts with CD155 expressed on antigen-presenting cells or tumour cells to down-regulate T cell and natural killer (NK) cell functions. TIGIT has emerged as a key inhibitor of anti-tumour responses that can hinder multiple steps of the cancer immunity cycle. Pre-clinical studies indicated that TIGIT blockade may protect against various solid and haematological cancers. Several monoclonal antibodies (mAbs) that block the inhibitory activity of human TIGIT have been developed. Clinical trials are ongoing, investigating TIGIT blockade as a monotherapy or in combination with anti-PD1/PD-L1 mAbs for the treatment of patients with advanced solid malignancies. In this review, we cover our current knowledge on TIGIT, from its discovery in 2009 to its current status as a clinical target.
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2326-6066.22544850
Abstract: Supplementary Figures 1-10
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2326-6066.C.6550764
Abstract: Abstract Dendritic cells (DC), the classic antigen-presenting cells of the immune system, switch from an adhesive, phagocytic phenotype in tissues, to a mature, nonadhesive phenotype that enables migration to lymph nodes to activate T cells and initiate antitumor responses. Monocyte-derived DCs are used in cancer immunotherapy, but their clinical efficacy is limited. Here, we show that cultured bone marrow–derived DCs (BM-DC) expressing dysfunctional β2-integrin adhesion receptors displayed enhanced tumor rejection capabilities in B16.OVA and B16-F10 melanoma models. This was associated with an increased CD8 sup + /sup T-cell response. BM-DCs expressing dysfunctional β2-integrins or manipulated to disrupt integrin adhesion or integrin/actin/nuclear linkages displayed spontaneous maturation in i ex vivo /i cultures (increased costimulatory marker expression, IL12 production, and 3D migration capabilities). This spontaneous maturation was associated with an altered DC epigenetic/transcriptional profile, including a global increase in chromatin accessibility and H3K4me3/H3K27me3 histone methylation. Genome-wide analyses showed that H3K4me3 methylation was increased on DC maturation genes, such as i CD86 /i , i Il12 /i , i Ccr7 /i , and i Fscn1 /i , and revealed a role for a transcription factor network involving Ikaros and RelA in the integrin-regulated phenotype of DCs. Manipulation of the integrin-regulated epigenetic landscape in wild-type i ex vivo /i –cultured BM-DCs enhanced their functionality in tumor rejection i in vivo /i . Thus, β2-integrin–mediated adhesion to the extracellular environment plays an important role in restricting DC maturation and antitumor responses through regulation of the cellular epigenetic and transcriptional landscape. Targeting β2-integrins could therefore be a new strategy to improve the performance of current DC-based cancer immunotherapies. /
Publisher: American Association for Cancer Research (AACR)
Date: 10-2017
DOI: 10.1158/1078-0432.CCR-17-0606
Abstract: Purpose: Novel partners for established immune checkpoint inhibitors in the treatment of cancer are needed to address the problems of primary and acquired resistance. The efficacy of combination RANKL and CTLA4 blockade in antitumor immunity has been suggested by recent case reports in melanoma. Here, we provide a rationale for this combination in mouse models of cancer. Experimental Design: The efficacy and mechanism of a combination of RANKL and CTLA4 blockade was examined by tumor-infiltrating lymphocyte analysis, tumor growth, and metastasis using a variety of neutralizing antibodies and gene-targeted mice. Results: RANKL blockade improved the efficacy of anti-CTLA4 mAbs against solid tumors and experimental metastases, with regulatory T-cell (Treg)–depleting anti-CTLA4 mAbs of the mouse IgG2a isotype showing greatest combinatorial activity. The optimal combination depended on the presence of activating Fc receptors and lymphocytes (NK cells for metastatic disease and predominantly CD8+ T cells for subcutaneous tumor control), whereas anti-RANKL alone did not require FcR. The significantly higher T-cell infiltration into solid tumors post anti-RANKL and anti-CTLA4 was accompanied by increased T-cell effector function (cytokine polyfunctionality), and anti-RANKL activity occurred independently of Treg depletion. The majority of RANKL expression in tumors was on T cells whereas RANK-expressing cells were mostly tumor-associated macrophages (TAM), with some expression also observed on dendritic cells (DC) and myeloid-derived suppressor cells (MDSC). Conclusions: These results provide a rationale for the further investigation of RANKL–RANK interactions in tumor immunity and a basis for development of translational markers of interest in human clinical trials. Clin Cancer Res 23(19) 5789–801. ©2017 AACR.
Publisher: American Society for Microbiology
Date: 11-2012
DOI: 10.1128/JB.00681-12
Abstract: We report the complete and annotated genome sequence of the plant-pathogenic enterobacterium Pectobacterium sp. strain SCC3193, a model strain isolated from potato in Finland. The Pectobacterium sp. SCC3193 genome consists of a 516,411-bp chromosome, with no plasmids.
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2326-6066.22544841.V1
Abstract: Supplementary Table 3
Publisher: Informa UK Limited
Date: 26-03-2018
Publisher: American Association for Cancer Research (AACR)
Date: 15-09-2016
DOI: 10.1158/0008-5472.CAN-16-0194
Abstract: New combination immunotherapies are displaying both efficacy and immune-related adverse events (irAE) in humans. However, grade 3/4 irAEs occur in a high proportion, which can lead to discontinuation of treatment and can result in fatalities if not promptly treated. Prolonged T regulatory cell (Treg) depletion in tumor-bearing Foxp3-DTR mice using diphtheria toxin (DT) mirrored the spectrum of antitumor responses and severity of irAEs that can occur in ipilimumab/nivolumab-treated patients. In contrast, transient Treg depletion or anti-CTLA-4/PD-1 therapy had equivalent effects in mice, lowering the immune tolerance threshold and allowing irAEs to be more easily induced following treatment with additional immunomodulatory antibodies. Transient Treg depletion of DT in combination with anti-PD-1 or anti-TIM-3 monoclonal antibodies had a high therapeutic window compared with DT plus anti-CD137. In contrast, DT plus anti-CD137–treated mice developed severe irAEs similar to grade 3/4 clinical symptoms. These irAEs appeared because of an infiltration of activated proliferating effector T cells in the tissues producing IFNγ and TNF however, TNF blockade decreased irAEs severity without impacting on tumor growth. Cancer Res 76(18) 5288–301. ©2016 AACR.
Publisher: American Association for Cancer Research (AACR)
Date: 31-07-2018
DOI: 10.1158/2326-6066.CIR-18-0011
Abstract: Tumor-induced immunosuppression is mediated through various mechanisms including engagement of immune checkpoint receptors on effector cells, function of immunoregulatory cells such as regulatory T cells and myeloid-derived suppressor cells, and deployment of immunosuppressive cytokines such as TGFβ and IL10. IL23 is a cytokine that negatively affects antitumor immunity. In this study, we investigated whether IL23-deficient (IL23p19−/−) and IL23R-deficient (IL23R−/−) mice phenocopied each other, with respect to their tumor control. We found that IL23R−/− mice had significantly fewer lung metastases compared with IL23p19−/− mice across three different experimental lung metastasis models (B16F10, LWT1, and RM-1). Similarly, IL23R blocking antibodies were more effective than antibodies neutralizing IL23 in suppressing experimental lung metastases. The antimetastatic activity of anti-IL23R was dependent on NK cells and IFNγ but independent of CD8+ T cells, CD4+ T cells, activating Fc receptors, and IL12. Furthermore, our data suggest this increased antitumor efficacy was due to an increase in the proportion of IFNγ-producing NK cells in the lungs of B16F10 tumor-bearing mice. Anti-IL23R, but not anti-IL23p19, partially suppressed lung metastases in tumor-bearing mice neutralized for IL12p40. Collectively, our data imply that IL23R has tumor-promoting effects that are partially independent of IL23p19. Blocking IL23R may be more effective than neutralizing IL23 in the suppression of tumor metastases. Cancer Immunol Res 6(8) 978–87. ©2018 AACR.
No related grants have been discovered for Heidi Harjunpää.