Immune cell constitution in the tumor microenvironment predicts the outcome in diffuse large B-cell lymphoma.

Abstract:

: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 lymphoma (DLBCL), and predict the outcome in response to immunochemotherapy. We profiled the expression of 730 immune-related genes in tumor tissues of 81 patients with DLBCL utilizing the Nanostring platform, and used multiplex immunohistochemistry to characterize T-cell phenotypes, including cytotoxic T-cells (CD8, Granzyme B, OX40, Ki67), T-cell immune checkpoint (CD3, CD4, CD8, PD1, TIM3, LAG3), as well as regulatory T-cells and Th1 effector cells (CD3, CD4, FOXP3, TBET) in 188 patients. We observed a high degree of heterogeneity at the transcriptome level. Correlation matrix analysis identified gene expression signatures with highly correlating genes - the main cluster containing genes for cytolytic factors, immune checkpoint molecules, T-cells and macrophages, together entitled as a TME immune cell signature. Immunophenotyping of the distinct cell subsets revealed that a high proportion of immune checkpoint positive T-cells translated to unfavorable survival. Together, our results demonstrate that the immunological profile of DLBCL TME is heterogeneous and clinically meaningful. This highlights the potential impact of T-cell immune checkpoint in regulating survival and resistance to immunochemotherapy.

journal_name

Haematologica

journal_title

Haematologica

authors

Autio M,Leivonen SK,Brück O,Mustjoki S,Jørgensen JM,Karjalainen-Lindsberg ML,Beiske K,Holte H,Pellinen T,Leppä S

doi

10.3324/haematol.2019.243626

subject

Has Abstract

pub_date

2020-02-20 00:00:00

eissn

0390-6078

issn

1592-8721

pii

haematol.2019.243626

pub_type

杂志文章
  • Immune reconstitution after autologous hematopoietic stem cell transplantation in relation to underlying disease, type of high-dose therapy and infectious complications.

    abstract:BACKGROUND AND OBJECTIVES:Autologous peripheral stem cell transplantation (APSCT) is increasingly used for various hematologic malignancies and solid tumors. The objective of this study was to analyze the immune reconstitution after APSCT and see if there was any correlation with diagnosis, age, type of high-dose thera...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:

    authors: Steingrimsdottir H,Gruber A,Björkholm M,Svensson A,Hansson M

    更新日期:2000-08-01 00:00:00

  • The putative role of transforming viruses in childhood acute lymphoblastic leukemia.

    abstract::Epidemiological evidence suggests that infection is involved in the etiology of common acute lymphoblastic leukemia, either by stimulating an inappropriate immune response or in the form of a classical transforming agent. In an attempt to elucidate the role that infection is playing in this disease, we used representa...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:

    authors: MacKenzie J,Greaves MF,Eden TO,Clayton RA,Perry J,Wilson KS,Jarrett RF

    更新日期:2006-02-01 00:00:00

  • Allogeneic hematopoietic stem cells from sources other than bone marrow: biological and technical aspects.

    abstract:BACKGROUND AND OBJECTIVE:Identification and characterization of hematopoietic stem cells in peripheral blood (PB) and cord blood (CB) have suggested feasible alternatives to conventional allogeneic bone marrow (BM) transplantation. The growing interest in this use of allogeneic stem cells has prompted the Working Group...

    journal_title:Haematologica

    pub_type: 杂志文章,评审

    doi:

    authors: Bertolini F,de Vincentiis A,Lanata L,Lemoli RM,Maccario R,Majolino I,Ponchio L,Rondelli D,Tabilio A,Zanon P,Tura S

    更新日期:1997-03-01 00:00:00

  • Nilotinib 300 mg twice daily: an academic single-arm study of newly diagnosed chronic phase chronic myeloid leukemia patients.

    abstract::The introduction and the extended clinical use of nilotinib in the first-line treatment of chronic myeloid leukemia have been based on company-sponsored trials. Independent confirmations are extremely important. We report an investigator-sponsored study of nilotinib 300 mg twice daily in 130 chronic myeloid leukemia p...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2016.144949

    authors: Castagnetti F,Breccia M,Gugliotta G,Martino B,D'Adda M,Stagno F,Carella AM,Avanzini P,Tiribelli M,Trabacchi E,Visani G,Gobbi M,Salvucci M,Levato L,Binotto G,Capalbo SF,Bochicchio MT,Soverini S,Cavo M,Martinelli G,

    更新日期:2016-10-01 00:00:00

  • Plasma thrombomodulin concentrations in infants and children undergoing cardiac catheterization.

    abstract::Circulating plasma thrombomodulin (TM) is an endothelial cell marker which may reflect endothelial injury. To find out to what extent diagnostic cardiac catheterization irritates vascular endothelium we conducted a prospective study in 91 children. Soluble TM concentrations, along with thrombin generation, were measur...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:

    authors: Vielhaber H,Kehl HG,Kececioglu D,Nowak-Göttl U

    更新日期:1996-09-01 00:00:00

  • Progression to acquired immunodeficiency syndrome in 94 human immunodeficiency virus-positive hemophiliacs with long-term follow-up.

    abstract:BACKGROUND AND OBJECTIVES:Human immunodeficiency virus (HIV) infection was transmitted to many hemophilics treated with non-inactivated factor concentrates before 1986. The aim of this study was to know the long-term incidence of AIDS and risk factors for its development in HIV-infected hemophiliacs. DESIGN AND METHOD...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:

    authors: Lorenzo JI,Moscardó F,López-Aldeguer J,Aznar JA

    更新日期:2001-03-01 00:00:00

  • The status of high-dose chemotherapy with hematopoietic stem cell transplantation in germ cell tumor patients.

    abstract:BACKGROUND AND OBJECTIVES:Germ cell tumors (GCTs) are very chemosensitive cancers, in which high-dose chemotherapy (HDCT) has been investigated as salvage therapy or as first-line treatment in poor prognosis patients. This paper presents an update of available information in order to define the status of HDCT in GCT pa...

    journal_title:Haematologica

    pub_type: 杂志文章,评审

    doi:

    authors: De Giorgi U,Rosti G,Papiani G,Marangolo M

    更新日期:2002-01-01 00:00:00

  • Low RPS14 expression is common in myelodysplastic syndromes without 5q- aberration and defines a subgroup of patients with prolonged survival.

    abstract::To further clarify the role of ribosomal protein S14 (RPS14) in myelodysplastic syndrome, we examined RPS14 transcription in bone marrow derived CD34+ cells from patients with non-5q- myelodysplastic syndrome and found a reduced expression of RPS14 in 51 of 72 (71%) patients. MDS patients with an intermediate-1 risk (...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2009.008508

    authors: Czibere A,Bruns I,Junge B,Singh R,Kobbe G,Haas R,Germing U

    更新日期:2009-10-01 00:00:00

  • Recovery of cord blood hematopoietic progenitors after successive freezing and thawing procedures.

    abstract:BACKGROUND AND OBJECTIVES:Cord blood (CB) is a valuable source of stem cells. Most CB units are still cryopreserved in single bags in the world's CB banks. Thawing a single CB unit, dividing it into two parts, expanding the smaller one and refreezing the other would optimize ex vivo expansion of CB progenitors prior to...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:

    authors: Timeus F,Crescenzio N,Saracco P,Doria A,Fazio L,Albiani R,Cordero Di Montezemolo L,Perugini L,Incarbone E

    更新日期:2003-01-01 00:00:00

  • Allogeneic stem cell transplantation for patients with acute myeloid leukemia or myelodysplastic syndrome who have chromosome 5 and/or 7 abnormalities.

    abstract:BACKGROUND AND OBJECTIVES:Chromosome 5 and/or 7 abnormalities are cytogenetic findings indicative of a poor prognosis in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). The only potential cure for such patients is allogeneic stem cell transplantation (SCT). As data on allogeneic SCT in thi...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:

    authors: van der Straaten HM,van Biezen A,Brand R,Schattenberg AV,Egeler RM,Barge RM,Cornelissen JJ,Schouten HC,Ossenkoppele GJ,Verdonck LF,Netherlands Stem Cell Transplant Registry \TYPHON\.

    更新日期:2005-10-01 00:00:00

  • Multilineage engraftment of refrozen cord blood hematopoietic progenitors in NOD/SCID mice.

    abstract::Seven cord blood (CB) units were tested for their capacity to repopulate irradiated NOD/SCID mice after one or two successive cryopreservation procedures. In primary transplants with frozen or refrozen CB cells we observed equivalent human colonies and percentages of human CD45+ cells, with multilineage engraftment. I...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:

    authors: Timeus F,Crescenzio N,Sanavio F,Fazio L,Doria A,Foglia L,Pignochino Y,Berger M,Piacibello W,Madon E,Cordero di Montezemolo L,Fagioli F

    更新日期:2006-03-01 00:00:00

  • Reduced intensity haplo plus single cord transplant compared to double cord transplant: improved engraftment and graft-versus-host disease-free, relapse-free survival.

    abstract::Umbilical cord blood stem cell transplants are commonly used in adults lacking HLA-identical donors. Delays in hematopoietic recovery contribute to mortality and morbidity. To hasten recovery, we used co-infusion of progenitor cells from a partially matched related donor and from an umbilical cord blood graft (haplo-c...

    journal_title:Haematologica

    pub_type: 临床试验,杂志文章

    doi:10.3324/haematol.2015.138594

    authors: van Besien K,Hari P,Zhang MJ,Liu HT,Stock W,Godley L,Odenike O,Larson R,Bishop M,Wickrema A,Gergis U,Mayer S,Shore T,Tsai S,Rhodes J,Cushing MM,Korman S,Artz A

    更新日期:2016-05-01 00:00:00

  • Metronomic therapy is an effective salvage treatment for heavily pre-treated relapsed/refractory multiple myeloma.

    abstract::Relapsed/refractory multiple myeloma represents a major challenge in multiple myeloma therapy. For patients with relapsed/refractory multiple myeloma, we developed a treatment schema of metronomically scheduled drug therapy. We identified 186 patients who had been treated with metronomic therapy between March 2004 and...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2013.085183

    authors: Papanikolaou X,Szymonifka J,Rosenthal A,Heuck CJ,Mitchell A,Johann D Jr,Keller J,Waheed S,Usmani SZ,Van Rhee F,Bailey C,Petty N,Hoering A,Crowley J,Barlogie B

    更新日期:2013-07-01 00:00:00

  • Aerobic glycolysis fuels platelet activation: small-molecule modulators of platelet metabolism as anti-thrombotic agents.

    abstract::Platelets are critical to arterial thrombosis, which underlies myocardial infarction and stroke. Activated platelets, regardless of the nature of their stimulus, initiate energy-intensive processes that sustain thrombus, while adapting to potential adversities of hypoxia and nutrient deprivation within the densely pac...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2018.205724

    authors: Kulkarni PP,Tiwari A,Singh N,Gautam D,Sonkar VK,Agarwal V,Dash D

    更新日期:2019-04-01 00:00:00

  • Genotypic heterogeneity may explain phenotypic variations in inherited factor VII deficiency.

    abstract::Inherited factor VIl (FVII) deficiency is a rare autosomal recessive coagulation disorder characterized by a wide genet-ic heterogeneity and a poor relationship between FVII activity (FVII:C) levels and severity of the hemorrhagic diathesis. Given both the rarity and the heterogeneity of this disorder,genotype-phenoty...

    journal_title:Haematologica

    pub_type: 信件

    doi:

    authors: Giansily-Blaizot M,Aguilar-Martinez P,Schved JF

    更新日期:2002-03-01 00:00:00

  • Inefficacy of fresh frozen plasma in the treatment of L-asparaginase-induced coagulation factor deficiencies during ALL induction therapy.

    abstract::A prospective longitudinal study was conducted to determine whether single-donor fresh frozen plasma (FFP) substitution was able to influence L-asparaginase-associated hypoproteinemia. Within a 36-month period, 20 of 42 children with ALL received a total of 42 prophylactic FFP doses at a median of 10 (5-20) mliter/kg ...

    journal_title:Haematologica

    pub_type: 临床试验,杂志文章

    doi:

    authors: Nowak-Göttl U,Rath B,Binder M,Hassel JU,Wolff J,Husemann S,Ritter J

    更新日期:1995-09-01 00:00:00

  • Salvage therapy with high-dose cytarabine and mitoxantrone in combination with all-trans retinoic acid and gemtuzumab ozogamicin in acute myeloid leukemia refractory to first induction therapy.

    abstract::Outcome of patients with primary refractory acute myeloid leukemia remains unsatisfactory. We conducted a prospective phase II clinical trial with gemtuzumab ozogamicin (3 mg/m(2) intravenously on day 1), all-trans retinoic acid (45 mg/m(2) orally on days 4-6 and 15 mg/m(2) orally on days 7-28), high-dose cytarabine (...

    journal_title:Haematologica

    pub_type: 杂志文章,多中心研究

    doi:10.3324/haematol.2015.141622

    authors: Hütter-Krönke ML,Benner A,Döhner K,Krauter J,Weber D,Moessner M,Köhne CH,Horst HA,Schmidt-Wolf IG,Rummel M,Götze K,Koller E,Petzer AL,Salwender H,Fiedler W,Kirchen H,Haase D,Kremers S,Theobald M,Matzdorff AC,Ganse

    更新日期:2016-07-01 00:00:00

  • Fractionated cyclophosphamide added to the IVAP regimen (idarubicin-vincristine-L-asparaginase-prednisone) could lower the risk of primary refractory disease in T-lineage but not B-lineage acute lymphoblastic leukemia: first results from a phase II clinic

    abstract:BACKGROUND AND OBJECTIVE:In a prior study, primary resistant acute lymphoblastic leukemia (RES-ALL) was observed in 11 of 176 (6%) adult patients treated with a four drug regimen (IVAP), its incidence being higher in T-cell or Philadelphia (Ph) chromosome/BCR-ABL rearrangement positive ALL cases with a blast cell count...

    journal_title:Haematologica

    pub_type: 临床试验,杂志文章,多中心研究

    doi:

    authors: Bassan R,Pogliani E,Lerede T,Fabris P,Rossi G,Morandi S,Casula P,Lambertenghi-Deliliers G,Vespignani M,Izzi T,Coser P,Corneo G,Barbui T

    更新日期:1999-12-01 00:00:00

  • A cooperative study of epirubicin with cyclophosphamide, vincristine and prednisone (CEOP) in non-Hodgkin's lymphoma.

    abstract:BACKGROUND:The purpose of our cooperative trial was to investigate whether epirubicin (EPI) at 90 mg/m2 in a CHOP-like combination (called CEOP) could increase complete response (CR) and survival rates in non-Hodgkin lymphoma (NHL) patients while maintaining a tolerable degree of toxicity. METHODS:Between September 19...

    journal_title:Haematologica

    pub_type: 临床试验,杂志文章,多中心研究

    doi:

    authors: Lambertenghi Deliliers G,Butti C,Baldini L,Ceriani A,Lombardi F,Luoni M,Montalbetti L,Pavia G,Pinotti G,Pogliani E

    更新日期:1995-07-01 00:00:00

  • Immunosuppressive therapy with anti-thymocyte globulin and cyclosporine A in selected children with hypoplastic refractory cytopenia.

    abstract::It is currently unknown whether immunosuppressive therapy or hematopoietic stem cell transplantation is the most appropriate treatment strategy for children with refractory cytopenia and normal karyotype or trisomy 8. We report on 31 children with hypoplastic refractory cytopenia treated with immunosuppressive therapy...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.10683

    authors: Yoshimi A,Baumann I,Führer M,Bergsträsser E,Göbel U,Sykora KW,Klingebiel T,Gross-Wieltsch U,van den Heuvel-Eibrink MM,Fischer A,Nöllke P,Niemeyer C

    更新日期:2007-03-01 00:00:00

  • Activity of everolimus (RAD001) in relapsed and/or refractory multiple myeloma: a phase I study.

    abstract::The mammalian target of rapamycin plays an important role in multiple myeloma. The allosteric mammalian target of rapamycin inhibitor everolimus has long been approved for immunosuppression and has shown activity in certain cancers. This investigator-initiated phase I trial explored the use of everolimus in relapsed a...

    journal_title:Haematologica

    pub_type: 杂志文章,多中心研究

    doi:10.3324/haematol.2014.116269

    authors: Günther A,Baumann P,Burger R,Kellner C,Klapper W,Schmidmaier R,Gramatzki M

    更新日期:2015-04-01 00:00:00

  • Niche TWIST1 is critical for maintaining normal hematopoiesis and impeding leukemia progression.

    abstract::The bone marrow microenvironment regulates normal and malignant hematopoiesis, but the underlying molecular mechanisms remain poorly defined. Using a chimeric mice model, we demonstrate that Twist1 deletion in the bone marrow microenvironment results in alteration of multiple niche cells as well as downregulated expre...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2018.190652

    authors: Liu X,Ma Y,Li R,Guo D,Wang N,Zhao Y,Yin J,Ren Q,Lin Y,Ma X

    更新日期:2018-12-01 00:00:00

  • Patient-derived anti-β2GP1 antibodies recognize a peptide motif pattern and not a specific sequence of residues.

    abstract::Antiphospholipid antibody syndrome is an autoimmune disease characterized by the presence of so-called antiphospholipid antibodies and clinical manifestations such as recurrent thromboembolic or pregnancy complications. Although the main antigenic determinant for antiphospholipid antibodies has been identified as the ...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2017.170381

    authors: de Moerloose P,Fickentscher C,Boehlen F,Tiercy JM,Kruithof EKO,Brandt KJ

    更新日期:2017-08-01 00:00:00

  • The interleukin-3 receptor CD123 targeted SL-401 mediates potent cytotoxic activity against CD34+CD123+ cells from acute myeloid leukemia/myelodysplastic syndrome patients and healthy donors.

    abstract::Diseases with clonal hematopoiesis such as myelodysplastic syndrome and acute myeloid leukemia have high rates of relapse. Only a small subset of acute myeloid leukemia patients are cured with chemotherapy alone. Relapse in these diseases occurs at least in part due to the failure to eradicate leukemic stem cells or h...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2018.188193

    authors: Mani R,Goswami S,Gopalakrishnan B,Ramaswamy R,Wasmuth R,Tran M,Mo X,Gordon A,Bucci D,Lucas DM,Mims A,Brooks C,Dorrance A,Walker A,Blum W,Byrd JC,Lozanski G,Vasu S,Muthusamy N

    更新日期:2018-08-01 00:00:00

  • Autosomal dominant C1149R von Willebrand disease: phenotypic findings and their implications.

    abstract:BACKGROUND:Mutation C1149R in the von Willebrand factor (VWF) gene has been thought to cause autosomal dominant severe type 1 von Willebrand disease (VWD). DESIGN AND METHODS:Eight patients from three unrelated families with this mutation were included in the present study who had distinct VWF abnormalities, not descr...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2008.003301

    authors: Pérez-Rodríguez A,García-Rivero A,Lourés E,López-Fernández MF,Rodríguez-Trillo A,Batlle J

    更新日期:2009-05-01 00:00:00

  • Corticosteroids can reverse severe imatinib-induced hepatotoxicity.

    abstract:BACKGROUND:Imatinib can induce severe hepatotoxicity, in 1-5% of CML patients, many of whom need permanent imatinib discontinuation. DESIGN AND RESULTS:We report 5 CML patients who developed grade 3-4 hepatotoxicity after 2-8 months in imatinib. Different aetiologies of liver damage were ruled out and toxicity recurre...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:

    authors: Ferrero D,Pogliani EM,Rege-Cambrin G,Fava C,Mattioli G,Dellacasa C,Campa E,Perfetti P,Fumagalli M,Boccadoro M

    更新日期:2006-06-01 00:00:00

  • Adding growth factors or interleukin-3 to erythropoietin has limited effects on anemia of transfusion-dependent patients with myelodysplastic syndromes unresponsive to erythropoietin alone.

    abstract:BACKGROUND AND OBJECTIVES:Recombinant erythropoietin (r-EPO) induces erythroid responses in patients affected by myelodysplastic syndromes (MDS). However, the response rate declines to 10-15% in MDS with substantial transfusion needs. Both in vitro and in vivo studies have suggested that the addition of growth factors ...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:

    authors: Musto P,Sanpaolo G,D'Arena G,Scalzulli PR,Matera R,Falcone A,Bodenizza C,Perla G,Carotenuto M

    更新日期:2001-01-01 00:00:00

  • Kasabach-Merritt syndrome associated with giant liver hemangioma: the effect of combined therapy with danaparoid sodium and tranexamic acid.

    abstract::n patients with Kasabach-Merritt syndrome (KMS), local activation of coagulation commonly results in disseminated intravascular coagulation (DIC). Progress of DIC is associated with 30-40% mortality as a result of uncontrollable hemorrhage. A 39-year-old woman with an enlarging giant liver hemangioma was diagnosed as ...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:

    authors: Ontachi Y,Asakura H,Omote M,Yoshida T,Matsui O,Nakao S

    更新日期:2005-11-01 00:00:00

  • t(X;14)(p11.4;q32.33) is recurrent in marginal zone lymphoma and up-regulates GPR34.

    abstract::Genetic events underlying pathogenesis of nodal and extranodal marginal zone lymphoma are not completely understood. We report here a novel t(X;14)(p11.4;q32.33) identified in 4 lymphoma cases: 2 with a mucosa-associated lymphoid tissue lymphoma, one with a nodal marginal zone lymphoma and one with gastric diffuse lar...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2011.052639

    authors: Baens M,Finalet Ferreiro J,Tousseyn T,Urbankova H,Michaux L,de Leval L,Dierickx D,Wolter P,Sagaert X,Vandenberghe P,De Wolf-Peeters C,Wlodarska I

    更新日期:2012-02-01 00:00:00

  • SRSF2-p95 hotspot mutation is highly associated with advanced forms of mastocytosis and mutations in epigenetic regulator genes.

    abstract::Mastocytosis is a rare and chronic disease with phenotypes ranging from indolent to severe. Prognosis for this disease is variable and very few biomarkers to predict disease evolution or outcome are currently known. We have performed comprehensive screening in our large cohort of mastocytosis patients for mutations pr...

    journal_title:Haematologica

    pub_type: 杂志文章,多中心研究

    doi:10.3324/haematol.2013.095133

    authors: Hanssens K,Brenet F,Agopian J,Georgin-Lavialle S,Damaj G,Cabaret L,Chandesris MO,de Sepulveda P,Hermine O,Dubreuil P,Soucie E

    更新日期:2014-05-01 00:00:00