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Amini, Rose-Marie
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Publications (10 of 62) Show all publications
Amini, R.-M., Enblad, G., Hollander, P., Laszlo, S., Eriksson, E., Gustafsson, K. A., . . . Thörn, I. (2019). Altered profile of immune regulatory cells in the peripheral blood of lymphoma patients. BMC Cancer, 19, Article ID 316.
Open this publication in new window or tab >>Altered profile of immune regulatory cells in the peripheral blood of lymphoma patients
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2019 (English)In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 19, article id 316Article in journal (Refereed) Published
Abstract [en]

Background: Regulatory immune cells may modulate the lymphoma microenvironment and are of great interest due to the increasing prevalence of treatment with immunotherapies in lymphoma patients. The aim was to explore the composition of different immune regulatory cell subsets in the peripheral blood of newly diagnosed lymphoma patients in relation to treatment outcome. Methods: Forty-three newly diagnosed patients with lymphoma were included in the study; 24 with high-grade B-cell lymphoma (HGBCL) and 19 with classical Hodgkin lymphoma (cHL). Peripheral blood was prospectively collected and immune regulatory cells were identified by multi-color flow cytometry and analyzed in relation to healthy blood donors and clinical characteristics and outcome. Results: The percentage of CD3-positive T-cells was lower (p=0.03) in the peripheral blood of lymphoma patients at diagnosis compared to healthy blood donors regardless of lymphoma subtype, although statistically, neither the percentage of monocytes (p=0.2) nor the T-cell/monocyte ratio (p=0.055) differed significantly. A significant decrease in the percentage of a subset of regulatory NK cells (CD7(+)/CD3(-)/CD56(bright)/CD16(dim/-)) was identified in the peripheral blood of lymphoma patients compared to healthy blood donors (p=0.003). Lymphoma patients also had more granulocytic myeloid-derived suppressor cells (MDSCs) (p=0.003) compared to healthy blood donors, whereas monocytic MDSCs did not differ significantly (p=0.07). A superior disease-free survival was observed for cHL patients who had an increase in the percentage of granulocytic MDSCs (p=0.04). Conclusions: An altered profile of immune cells in the peripheral blood with a decrease in T-cells and regulatory NK-cells was observed in newly diagnosed lymphoma patients. CHL patients with higher percentages of regulatory NK cells and higher percentages of granulocytic MDSCs might have a better outcome, although the number of patients was low.

Place, publisher, year, edition, pages
BMC, 2019
Keywords
Immune regulatory cells, NK cells, T cells, Myeloid derived suppressor cells, High-grade B cell lymphoma, Hodgkin lymphoma
National Category
Cancer and Oncology Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-382563 (URN)10.1186/s12885-019-5529-0 (DOI)000463739000007 ()30953461 (PubMedID)
Available from: 2019-05-03 Created: 2019-05-03 Last updated: 2020-01-03Bibliographically approved
Abdulla, M., Hollander, P., Pandzic, T., Mansouri, L., Ednersson, S. B., Andersson, P.-O., . . . Amini, R.-M. (2019). Cell-of-origin determined by both gene expression profiling and immunohistochemistry is the strongest predictor of survival in patients with diffuse large B-cell lymphoma. American Journal of Hematology
Open this publication in new window or tab >>Cell-of-origin determined by both gene expression profiling and immunohistochemistry is the strongest predictor of survival in patients with diffuse large B-cell lymphoma
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2019 (English)In: American Journal of Hematology, ISSN 0361-8609, E-ISSN 1096-8652Article in journal (Refereed) Epub ahead of print
Abstract [en]

The tumor cells in diffuse large B-cell lymphomas (DLBCL) are considered to originate from germinal center derived B-cells (GCB) or activated B-cells (ABC). Gene expression profiling (GEP) is preferably used to determine the cell of origin (COO). However, GEP is not widely applied in clinical practice and consequently, several algorithms based on immunohistochemistry (IHC) have been developed. Our aim was to evaluate the concordance of COO assignment between the Lymph2Cx GEP assay and the IHC-based Hans algorithm, to decide which model is the best survival predictor. Both GEP and IHC were performed in 359 homogenously treated Swedish and Danish DLBCL patients, in a retrospective multicenter cohort. The overall concordance between GEP and IHC algorithm was 72%; GEP classified 85% of cases assigned as GCB by IHC, as GCB, while 58% classified as non-GCB by IHC, were categorized as ABC by GEP. There were significant survival differences (overall survival and progression-free survival) if cases were classified by GEP, whereas if cases were categorized by IHC only progression-free survival differed significantly. Importantly, patients assigned as non-GCB/ABC both by IHC and GEP had the worst prognosis, which was also significant in multivariate analyses. Double expression of MYC and BCL2 was more common in ABC cases and was associated with a dismal outcome. In conclusion, to determine COO both by IHC and GEP is the strongest outcome predictor to identify DLBCL patients with the worst outcome.

National Category
Hematology Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-397669 (URN)10.1002/ajh.25666 (DOI)000495085000001 ()31659781 (PubMedID)
Funder
Swedish Cancer SocietySwedish Research Council
Available from: 2019-11-28 Created: 2019-11-28 Last updated: 2020-01-31Bibliographically approved
Xochelli, A., Bikos, V., Polychronidou, E., Galigalidou, C., Agathangelidis, A., Charlotte, F., . . . Stamatopoulos, K. (2019). Disease-biased and shared characteristics of the immunoglobulin gene repertoires in marginal zone B cell lymphoproliferations. Journal of Pathology, 247(4), 416-421
Open this publication in new window or tab >>Disease-biased and shared characteristics of the immunoglobulin gene repertoires in marginal zone B cell lymphoproliferations
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2019 (English)In: Journal of Pathology, ISSN 0022-3417, E-ISSN 1096-9896, Vol. 247, no 4, p. 416-421Article in journal (Refereed) Published
Abstract [en]

The B cell receptor immunoglobulin (Ig) gene repertoires of marginal zone (MZ) lymphoproliferations were analyzed in order to obtain insight into their ontogenetic relationships. Our cohort included cases with MZ lymphomas (n = 488), i.e. splenic (SMZL), nodal (NMZL) and extranodal (ENMZL), as well as provisional entities (n = 76), according to the WHO classification. The most striking Ig gene repertoire skewing was observed in SMZL. However, restrictions were also identified in all other MZ lymphomas studied, particularly ENMZL, with significantly different Ig gene distributions depending on the primary site of involvement. Cross-entity comparisons of the MZ Ig sequence dataset with a large dataset of Ig sequences (MZ-related or not; n = 65 837) revealed four major clusters of cases sharing homologous ('public') heavy variable complementarity-determining region 3. These clusters included rearrangements from SMZL, ENMZL (gastric, salivary gland, ocular adnexa), chronic lymphocytic leukemia, but also rheumatoid factors and non-malignant splenic MZ cells. In conclusion, different MZ lymphomas display biased immunogenetic signatures indicating distinct antigen exposure histories. The existence of rare public stereotypes raises the intriguing possibility that common, pathogen-triggered, immune-mediated mechanisms may result in diverse B lymphoproliferations due to targeting versatile progenitor B cells and/or operating in particular microenvironments.

Place, publisher, year, edition, pages
WILEY, 2019
Keywords
marginal zone lymphoma, ontogeny, immunoglobulin gene, antigen
National Category
Cancer and Oncology Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-379880 (URN)10.1002/path.5209 (DOI)000460465000003 ()30484876 (PubMedID)
Funder
EU, Horizon 2020, 692298EU, Horizon 2020, LQ1601Swedish Cancer SocietySwedish Research CouncilKnut and Alice Wallenberg FoundationErik, Karin och Gösta Selanders Foundation
Available from: 2019-03-26 Created: 2019-03-26 Last updated: 2020-01-03Bibliographically approved
Pedersen, M. A., Gormsen, L. C., Kamper, P., Wassberg, C., Andersen, M. D., d'Amore, A. L., . . . d'Amore, F. (2019). Focal skeletal FDG uptake indicates poor prognosis in cHL regardless of extent and first-line chemotherapy. British Journal of Haematology, 186(3), 431-439
Open this publication in new window or tab >>Focal skeletal FDG uptake indicates poor prognosis in cHL regardless of extent and first-line chemotherapy
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2019 (English)In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 186, no 3, p. 431-439Article in journal (Refereed) Published
Abstract [en]

F-18-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) is used for staging classical Hodgkin lymphoma (cHL) with high sensitivity for skeletal involvement. However, it is unclear whether a single bone lesion carries the same adverse prognosis as multifocal lesions and if this is affected by type of chemotherapy [ABVD (adriamycin, bleomycin, vincristine, dacarbazine) versus BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone)]. We reviewed the clinico-pathological and outcome data from 209 patients with newly diagnosed cHL staged by FDG-PET/CT. Patterns of skeletal/bone marrow uptake (BMU) were divided into 'low' and 'high' diffuse BMU (i.e. without focal lesions), and unifocal or multifocal lesions. Additional separate survival analysis was performed, taking type of chemotherapy into account. Forty patients (19 center dot 2%) had skeletal lesions (20 unifocal, 20 multifocal). The 3-year progression-free-survival (PFS) was 80% for patients with 'low BMU', 87% for 'high BMU', 69% for 'unifocal' and 51% for 'multifocal' lesions; median follow-up was 38 months. The presence of bone lesions, both uni- and multifocal, was associated with significantly inferior PFS (log rank P = 0 center dot 0001), independent of chemotherapy type. Thus, increased diffuse BMU should not be considered as a risk factor in cHL, whereas unifocal or multifocal bone lesions should be regarded as important predictors of adverse outcome, irrespective of the chemotherapy regimen used.

Place, publisher, year, edition, pages
WILEY, 2019
Keywords
F-18-FDG PET, CT, classical Hodgkin lymphoma, bone marrow uptake, focal bone lesions, chemotherapy
National Category
Hematology Cancer and Oncology Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-393747 (URN)10.1111/bjh.15933 (DOI)000481501200007 ()31115045 (PubMedID)
Available from: 2019-11-11 Created: 2019-11-11 Last updated: 2020-01-03Bibliographically approved
Gholiha, A. R., Hollander, P., Hedström, G., Sundström, C., Molin, D., Smedby, K. E., . . . Enblad, G. (2019). High tumour plasma cell infiltration reflects an important microenvironmental component in classic Hodgkin lymphoma linked to presence of B-symptoms. British Journal of Haematology, 184(2), 192-201
Open this publication in new window or tab >>High tumour plasma cell infiltration reflects an important microenvironmental component in classic Hodgkin lymphoma linked to presence of B-symptoms
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2019 (English)In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 184, no 2, p. 192-201Article in journal (Refereed) Published
Abstract [en]

Plasma cells are important prognostic actors in different malignancies. The tumour microenvironmental composition in classic Hodgkin lymphoma (cHL) is a major prognostic key element; however, clinicopathological studies regarding plasma cells in cHL are lacking. The aim of this study was to investigate CD138+ (also termed SDC1+) plasma cell and IgG4 producing (IgG4+) plasma cells infiltration in the microenvironment of cHL. Immunohistochemistry with anti-CD138 and IgG4 antibodies was performed on diagnostic tumour biopsies from 124 patients with cHL, on tissue micro array (TMA). In 120 cases, CD138+ plasma cell-infiltration was associated with the presence of B-symptoms (P = 0·028) and advanced stage, IIB-IVB (P = 0·009). In multivariate analysis, CD138+ plasma cells correlated with eosinophil infiltration (P = 0·013). The subgroup of IgG4+ plasma cells was analysed in 122 cases and only correlated to CD138+ plasma cells (P = 0·004). Patients with high proportion of tumour infiltrating CD138+ plasma cells (defined as ≥10%), had a more inferior event-free survival (P = 0·007) and overall survival (P = 0·004) than patients with a low proportion of infiltrating CD138+ plasma cells (<10%), although significance was not maintained in multivariate analysis. In summary, a high proportion of tumour-associated plasma cells in cHL reflect an important component in the microenvironment of cHL.

Keywords
CD138 plasma cells, Hodgkin's lymphoma, IgG4-producing plasma cells, Syndecan-1, tumour microenvironment
National Category
Cancer and Oncology Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-372809 (URN)10.1111/bjh.15703 (DOI)000455218700009 ()30506671 (PubMedID)
Available from: 2019-01-09 Created: 2019-01-09 Last updated: 2020-01-08Bibliographically approved
Grootens, J., Ungerstedt, J. S., Ekoff, M., Rönnberg, E., Klimkowska, M., Amini, R.-M., . . . Dahlin, J. S. (2019). Single-cell analysis reveals the KIT D816V mutation in haematopoietic stem and progenitor cells in systemic mastocytosis. EBioMedicine, 43, 150-158
Open this publication in new window or tab >>Single-cell analysis reveals the KIT D816V mutation in haematopoietic stem and progenitor cells in systemic mastocytosis
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2019 (English)In: EBioMedicine, E-ISSN 2352-3964, Vol. 43, p. 150-158Article in journal (Refereed) Published
Abstract [en]

Background: Systemic mastocytosis (SM) is a haematological disease characterised by organ infiltration by neoplastic mast cells. Almost all SM patients have a mutation in the gene encoding the tyrosine kinase receptor KIT causing a D816V substitution and autoactivation of the receptor. Mast cells and CD34(+) haematopoietic progenitors can carry the mutation: however, in which progenitor cell subset the mutation arises is unknown. We aimed to investigate the distribution of the D816V mutation in single mast cells and single haematopoietic stem and progenitor cells.

Methods: Fluorescence-activated single-cell index sorting and KIT D816V mutation assessment were applied to analyse mast cells and >10,000 CD34(+) bone marrow progenitors across 10 haematopoietic progenitor subsets. In vitro assays verified cell-forming potential.

Findings: We found that in SM 60-99% of the mast cells harboured the KIT D816V mutation. Despite increased frequencies of mast cells in SM patients compared with control subjects, the haematopoietic progenitor subset frequencies were comparable. Nevertheless, the mutation could be detected throughout the haematopoietic landscape of SM patients, from haematopoietic stem cells to more lineage-primed progenitors. In addition, we demonstrate that Fc epsilon RI+ bone marrow progenitors exhibit mast cell-forming potential, and we describe aberrant CD45RA expression on SM mast cells for the first time.

Interpretation: The KIT D816V mutation arises in early haematopoietic stem and progenitor cells and the mutation frequency is approaching 100% in mature mast cells, which express the aberrant marker CD45RA.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE BV, 2019
Keywords
Systemic Mastocytosis, Single-cell, Mast cell, Mast cell progenitor, CD45RA, Haematopoiesis, Haematopoietic stem cells, KIT D816V
National Category
Cell and Molecular Biology Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-387962 (URN)10.1016/j.ebiom.2019.03.089 (DOI)000470091600028 ()30975542 (PubMedID)
Funder
Swedish Research CouncilSwedish Cancer SocietyThe Cancer Research Funds of RadiumhemmetMagnus Bergvall FoundationTore Nilsons Stiftelse för medicinsk forskningStockholm County Council
Available from: 2019-06-27 Created: 2019-06-27 Last updated: 2020-01-03Bibliographically approved
Bremer, T., Whitworth, P. W., Patel, R., Savala, J., Barry, T., Lyle, S., . . . Wärnberg, F. (2018). A Biological Signature for Breast Ductal Carcinoma In Situ to Predict Radiotherapy Benefit and Assess Recurrence Risk. Clinical Cancer Research, 24(23), 5895-5901
Open this publication in new window or tab >>A Biological Signature for Breast Ductal Carcinoma In Situ to Predict Radiotherapy Benefit and Assess Recurrence Risk
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2018 (English)In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 24, no 23, p. 5895-5901Article in journal (Refereed) Published
Abstract [en]

Purpose: Ductal carcinoma in situ (DCIS) patients and their physicians currently face challenging treatment decisions with limited information about the individual's subsequent breast cancer risk or treatment benefit. The DCI-SionRT biological signature developed in this study provides recurrence risk and predicts radiotherapy (RT) benefit for DCIS patients following breast-conserving surgery (BCS). Experimental Design: A biological signature that calculates an individualized Decision Score (DS) was developed and cross-validated in 526 DCIS patients treated with BCS = RT. The relationship was assessed between DS and 10-year risk of invasive breast cancer (IBC) or any ipsilateral breast event (IBE), including IBC or DCIS. RT benefit was evaluated by risk group and as a function of DS. Results: The DS was significantly associated with IBC and IBE risk, HR (per 5 units) of 4.2 and 3.1, respectively. For patients treated without RT, DS identified a Low Group with 10-year IBC risk of 4% (7% IBE) and an Elevated Risk Group with IBC risk of 15% (23% IBE). In analysis of DS and RT by group, the Elevated Risk Group received significant RT benefit, HR of 0.3 for IBC and IBE. In a clinicopathologically low-risk subset, DS reclassified 42% of patients into the Elevated Risk Group. In an interaction analysis of DS and RT, patients with elevated DS had significant RT benefit over baseline. Conclusions: The DS was prognostic for risk and predicted RT benefit for DCIS patients. DS identified a clinically meaningful low-risk group and a group with elevated 10-year risks that received substantial RT benefit over baseline.

National Category
Cancer and Oncology Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-372771 (URN)10.1158/1078-0432.CCR-18-0842 (DOI)000452374700013 ()30054280 (PubMedID)
Available from: 2019-01-14 Created: 2019-01-14 Last updated: 2019-03-29Bibliographically approved
Enblad, G., Karlsson, H., Gammelgård, G., Wenthe, J., Lövgren, T., Amini, R.-M., . . . Loskog, A. (2018). A Phase I/IIa Trial Using CD19-Targeted Third-Generation CAR T Cells for Lymphoma and Leukemia. Clinical Cancer Research, 24(24), 6185-6194
Open this publication in new window or tab >>A Phase I/IIa Trial Using CD19-Targeted Third-Generation CAR T Cells for Lymphoma and Leukemia
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2018 (English)In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 24, no 24, p. 6185-6194Article in journal (Refereed) Published
Abstract [en]

Purpose: The chimeric antigen receptor (CAR) T-cell therapy has been effective for patients with CD19(+) B-cell malignancies. Most studies have investigated the second-generation CARs with either CD28 or 4-1BB costimulatory domains in the CAR receptor. Here, we describe the first clinical phase I/IIa trial using third-generation CAR T cells targeting CD19 to evaluate safety and efficacy.

Patients and Methods: Fifteen patients with B-cell lymphoma or leukemia were treated with CAR T cells. The patients with lymphoma received chemotherapy during CAR manufacture and 11 of 15 were given low-dose cyclophosphamide and fludarabine conditioning prior to CAR infusion. Peripheral blood was sampled before and at multiple time points after CAR infusion to evaluate the persistence of CAR T cells and for immune profiling, using quantitative PCR, flow cytometry, and a proteomic array.

Results: Treatment with third-generation CAR T cells was generally safe with 4 patients requiring hospitalization due to adverse reactions. Six of the 15 patients had initial complete responses [4/11 lymphoma and 2/4 acute lymphoblastic leukemia (ALL)], and 3 of the patients with lymphoma were in remission at 3 months. Two patients are still alive. Best predictor of response was a good immune status prior to CAR infusion with high IL12, DC-Lamp, Fas ligand, and TRAIL. Responding patients had low monocytic myeloid-derived suppressor cells (MDSCs; CD14(+)CD33(+)HLA(-)DR(-)) and low levels of IL6, IL8, NAP3, sPDL1, and sPDL2.

Conclusions: Third-generation CARs may be efficient in patients with advanced B-cell lymphoproliferative malignancy with only modest toxicity. Immune profiling pre- and posttreatment can be used to find response biomarkers.

National Category
Cancer and Oncology Hematology Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-372924 (URN)10.1158/1078-0432.CCR-18-0426 (DOI)000453267600012 ()30097433 (PubMedID)
Funder
Swedish Research CouncilAFA InsuranceSwedish Cancer Society
Available from: 2019-01-10 Created: 2019-01-10 Last updated: 2019-03-29Bibliographically approved
Hollander, P., Rostgaard, K., Ekström-Smedby, K., Molin, D., Loskog, A., de Nully Brown, P., . . . Glimelius, I. (2018). An anergic immune signature in the tumor microenvironment of classical Hodgkin lymphoma is associated with inferior outcome. European Journal of Haematology, 100(1), 88-97
Open this publication in new window or tab >>An anergic immune signature in the tumor microenvironment of classical Hodgkin lymphoma is associated with inferior outcome
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2018 (English)In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 100, no 1, p. 88-97Article in journal (Refereed) Published
Abstract [en]

Objective: The classical Hodgkin lymphoma (cHL) tumor microenvironment shows anongoing inflammatory response consisting of varying degrees of infiltrating eosinophils,mast cells, macrophages, regulatory T lymphocytes (Tregs), and activated lymphocytes surrounding the malignant cells. Herein, different immune signatures are characterized and correlated with treatment outcome.

Methods: Tumor-infiltrating leukocytes were phenotyped in biopsies from 459 patients with cHL. Time to progression (TTP) (primary progression, relapse, or death from cHL) and overall survival were analyzed using Cox proportional hazards regression.

Results: The leukocyte infiltration in the microenvironment was highly diverse between patients and was categorized in 4 immune signatures (active, anergic, innate, or mixed). A high proportion of Tregs (anergic) resulted in shorter TTP (median 12.9-year follow-up) in age-adjusted analyses (hazard ratio = 1.82; 95% confidence interval 1.05-3-15). Epstein-Barrvirus (EBV)-positive cases had higher proportions of macrophages and activated lymphocytes than EBV negative, but neither of those leukocytes predicted prognosis.

Conclusions: Abundant Tregs (anergic signature) indicate a shorter TTP, particularly in younger patients. This is probably due to a reduced ability of the immune system to attack the tumor cells. Our data warrant further investigation if these suggested immune signatures could predict outcome of immunotherapy such as immune checkpoint inhibitors.

Keywords
Hodgkin lymphoma, Regulatory T lymphocytes, Tumor microenvironment
National Category
Cancer and Oncology Clinical Laboratory Medicine
Research subject
Pathology; Oncology
Identifiers
urn:nbn:se:uu:diva-335491 (URN)10.1111/ejh.12987 (DOI)000418451500012 ()29064587 (PubMedID)
Funder
Swedish Cancer Society, CAN 2016/440, CAN 2016/607, CAN 2016/552
Available from: 2017-12-06 Created: 2017-12-06 Last updated: 2019-04-02Bibliographically approved
Hollander, P., Amini, R.-M., Ginman, B., Molin, D., Enblad, G. & Glimelius, I. (2018). Expression of PD-1 and PD-L1 increase in consecutive biopsies in patients with classical Hodgkin lymphoma. PLoS ONE, 13(9), Article ID e0204870.
Open this publication in new window or tab >>Expression of PD-1 and PD-L1 increase in consecutive biopsies in patients with classical Hodgkin lymphoma
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2018 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 9, article id e0204870Article in journal (Refereed) Published
Abstract [en]

High expression of programmed death receptor 1 (PD-1) and its ligand (PD-L1) by leukocytes in primary classical Hodgkin lymphoma (cHL) is associated with inferior outcome. However, it is unclear how expression varies during disease progression, and in the event of relapse. Our aim was to study PD-1 and PD-L1 in consecutive biopsies from untreated and treated cHL patients. We screened pathology registries from 3500 cHL patients. Eleven patients had a diagnostic cHL biopsy and a previous benign lymph node biopsy reclassified as cHL when reviewed and designated as the untreated. Thirty patients had a primary and a relapse biopsy, designated as the treated. Biopsies were immunostained to detect PD-1+ and PD-L1+ leukocytes, and PD-L1+ tumor cells. In the untreated, none of the markers were statistically significantly different when biopsies 1 and 2 were compared. In the treated, 19, 22, and 18 of 30 cases had increased proportions of PD-1+ leukocytes, PD-L1+ leukocytes and PD-L1+ tumor cells, respectively, and were all statistically significantly increased when primary and relapse biopsies were compared. PD-1 and PD-L1 most likely increase due to primary treatment with chemotherapy and radiotherapy, which could have implications regarding treatment with PD-1 inhibitors.

National Category
Cancer and Oncology Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-372644 (URN)10.1371/journal.pone.0204870 (DOI)000445907400111 ()
Funder
Swedish Cancer Society
Available from: 2019-01-08 Created: 2019-01-08 Last updated: 2019-06-26Bibliographically approved
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