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Interferon follicular lymphoma

Akinori Hirai, Naing Ye Aung, Rintaro Ohe, Akiko Nishida, Tomoya Kato, Hongxue Meng, Kenichi Ishizawa, Junichi Fujii, Mitsunori Yamakawa
Transient receptor potential melastatin 8 (TRPM8) is a member of the transient receptor potential superfamily of Ca2+ channels. The aim of the present study was to clarify TRPM8 expression in reactive lymphoid tissues and mature B-cell neoplasms. Reactive and neoplastic lymphoid tissues were used to evaluate TRPM8 expression by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). TRPM8+ cells were frequently detected in the follicular light zone and marginal zone of reactive lymphoid tissues...
November 2018: Oncology Letters
Sandra Lockmer, Bjørn Østenstad, Hans Hagberg, Harald Holte, Ann-Sofie Johansson, Björn Engelbrekt Wahlin, Karin Fahl Wader, Chloé Beate Steen, Peter Meyer, Martin Maisenhølder, Karin Ekström Smedby, Peter Brown, Eva Kimby
PURPOSE: For indolent lymphoma, the optimal timing, sequence, and choice of therapeutic regimens remain a matter of debate. In two Nordic Lymphoma Group randomized trials, symptomatic or clearly progressing patients were treated first line with a rituximab-containing regimen without chemotherapy. The purpose of this study was to assess long-term survival, risk of transformation, and need of new therapies. METHODS: Data were collected at cross-sectional follow-up for 321 patients with indolent lymphoma (84% with follicular lymphomas [FL]) included in one of two Nordic Lymphoma Group trials (accrual 1998 to 1999 and 2002 to 2008)...
October 4, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Kieu-Suong Le, Patricia Amé-Thomas, Karin Tarte, Françoise Gondois-Rey, Samuel Granjeaud, Florence Orlanducci, Etienne D Foucher, Florence Broussais, Reda Bouabdallah, Thierry Fest, Dominique Leroux, Sapna Yadavilli, Patrick A Mayes, Luc Xerri, Daniel Olive
A better characterization of T-cell subsets in the microenvironment of classical Hodgkin lymphoma (cHL) would help to develop immunotherapies. Using multicolor flow cytometry, we identified in 6 of 43 cHL tissue samples a previously unrecognized subset of CD8 T cells coexpressing CXCR5 and inducible T-cell costimulator (ICOS) molecules (CD8CXCR5+ICOS+ ). These cells shared phenotypic features with follicular helper T (TFH ) cells including low CCR7 expression together with high expression of B-cell lymphoma-6, programmed cell death 1, B and T lymphocyte attenuator, CD200, and OX40...
August 14, 2018: Blood Advances
Ajay K Gopal, Stephen J Schuster, Nathan H Fowler, Judith Trotman, Georg Hess, Jing-Zhou Hou, Abdulraheem Yacoub, Michael Lill, Peter Martin, Umberto Vitolo, Andrew Spencer, John Radford, Wojciech Jurczak, James Morton, Dolores Caballero, Sanjay Deshpande, Gary J Gartenberg, Shean-Sheng Wang, Rajendra N Damle, Michael Schaffer, Sriram Balasubramanian, Jessica Vermeulen, Bruce D Cheson, Gilles Salles
Purpose The Bruton's tyrosine kinase inhibitor ibrutinib has demonstrated clinical activity in B-cell malignancies. The DAWN study assessed the efficacy and safety of single-agent ibrutinib in chemoimmunotherapy relapsed/refractory follicular lymphoma (FL) patients. Methods DAWN was an open-label, single-arm, phase II study of ibrutinib in patients with FL with two or more prior lines of therapy. Patients received ibrutinib 560 mg daily until progressive disease/unacceptable toxicity. The primary objective was independent review committee-assessed overall response rate (ORR; complete response plus partial response)...
August 10, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Anuj Verma, Sridhar Epari, Sumeet Gujral, Tanuja Shet
Rearrangements involving interferon regulatory factor 4 (IRF4) gene has been recently described in a subtype of diffuse large B-cell lymphoma (DLBCL). They occur in a typical clinical setting of a pediatric age group, predominantly with tonsillar mass, usually as a low-stage disease and with good response to chemotherapy. Histomorphologically, they show nodular/follicular architecture with diffuse strong immunopositivity for multiple myeloma oncogene 1. Here, the authors describe one such unusual case of large B-cell lymphoma with IRF4 gene rearrangement in a young child with the unusual location of inguinal region and detailed pathological (histological, immunohistochemical, and molecular) findings...
April 2018: Indian Journal of Pathology & Microbiology
Janine Schmidt, Joan Enric Ramis-Zaldivar, Ferran Nadeu, Blanca Gonzalez-Farre, Alba Navarro, Caoimhe Egan, Ivonne Aidee Montes-Mojarro, Teresa Marafioti, Jose Cabeçadas, Jon van der Walt, Stefan Dojcinov, Andreas Rosenwald, German Ott, Irina Bonzheim, Falko Fend, Elias Campo, Elaine S Jaffe, Itziar Salaverria, Leticia Quintanilla-Martinez
Pediatric-type follicular lymphoma (PTFL) is a B-cell lymphoma with distinctive clinicopathological features. Recently, recurrent genetic alterations of potential importance for its pathogenesis that disrupt pathways associated with the germinal center reaction ( TNFRSF14 , IRF8 ), immune escape ( TNFRSF14 ), and anti-apoptosis ( MAP2K1 ) have been described. In an attempt to shed more light onto the pathogenesis of PTFL, an integrative analysis of these mutations was undertaken in a large cohort of 43 cases previously characterized by targeted next-generation sequencing and copy number array...
July 20, 2017: Blood
Junjie Xing, Chenxin Zhang, Xiaohong Yang, Shaoxuan Wang, Zhongchuan Wang, Xu Li, Enda Yu
Colorectal cancer is the third most prevalent cancer type worldwide and contributes to a significant percentage of cancer-related mortality. Recent studies have shown that the CXCR5+ CD8+ T cells present more potent proinflammatory function than CXCR5- CD8+ T cells in chronic virus infections and in follicular lymphoma, but the role of CXCR5+ CD8+ T cells in colorectal cancer is yet unclear. In this study, we demonstrated that CXCR5+ CD8+ T cells were very rare in peripheral blood mononuclear cells from healthy and colorectal cancer individuals, but were significantly enriched in resected tumors and tumor-associated lymph nodes...
July 1, 2017: Experimental Cell Research
Hong Qiu, Haijing Wu, Vera Chan, Chak-Sing Lau, Qianjin Lu
T-follicular helper (Tfh) cells are a specialized subset of T cells that provide help to B cells and promote the formation of germinal centers (GCs). Tfh cells transmit important signals to B cells that drive class switch recombination, somatic hyper-mutation, the generation of high-affinity antibodies, immunological memory and their differentiation into plasma cells or memory B cells in the GCs. Tfh-cell differentiation is regulated by the coordinated functions of distinct cytokines, including interleukin (IL)-6, IL-21, IL-12, IL-23, IL-2, IL-7 and transforming growth factor-β (TGF-β), as well as transcription factors, including B-cell lymphoma 6 protein (Bcl-6), Signal transducers and activators of transcription (STAT)1, STAT3, STAT4, B-cell activating transcription factor (Batf), interferon regulatory factor 4 (IRF4), v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog (C-Maf), T-cell-specific transcription factor 1 (TCF-1) and Achaete-scute homolog 2 (Acl2), which have been shown to form a complex transcriptional network...
March 2017: Autoimmunity
Luca Arcaini, Caroline Besson, Marco Frigeni, Hélène Fontaine, Maria Goldaniga, Milvia Casato, Marcella Visentini, Harrys A Torres, Veronique Loustaud-Ratti, Jan Peveling-Oberhag, Paolo Fabris, Roberto Rossotti, Francesco Zaja, Luigi Rigacci, Sara Rattotti, Raffaele Bruno, Michele Merli, Céline Dorival, Laurent Alric, Arnaud Jaccard, Stanislas Pol, Fabrice Carrat, Virginia Valeria Ferretti, Carlo Visco, Olivier Hermine
Regression of hepatitis C virus (HCV)-associated lymphoma with interferon (IFN)-based antiviral treatment supports an etiological link between lymphoma and HCV infection. In addition, a favorable impact of antiviral treatment on overall survival of patients with HCV-related lymphoma has been reported. Data on IFN-free regimens combining direct-acting antivirals (DAAs) in HCV-associated lymphoproliferative disorders are scanty. We analyzed the virological and lymphoproliferative disease response (LDR) of 46 patients with indolent B-cell non-Hodgkin lymphomas (NHLs) or chronic lymphocytic leukemia (CLL) and chronic HCV infection treated with DAAs...
November 24, 2016: Blood
Romeo-Gabriel Mihăilă
The hepatitis C virus (HCV) infected patients are prone to develop bone marrow or various tissue infiltrates with monoclonal B cells, monoclonal B lymphocytosis or different types of B cell non-Hodgkin's lymphoma (BCNHL), of which the most common are splenic marginal zone BCNHL, diffuse large BCNHL and follicular lymphoma. The association between chronic HCV infection and non Hodgkin's lymphoma has been observed especially in areas with high prevalence of this viral infection. Outside the limitations of some studies that have been conducted, there are also geographic, environmental, and genetic factors that contribute to the epidemiological differences...
July 21, 2016: World Journal of Gastroenterology: WJG
Michael G Ozawa, Aparna Bhaduri, Karen M Chisholm, Steven A Baker, Lisa Ma, James L Zehnder, Sandra Luna-Fineman, Michael P Link, Jason D Merker, Daniel A Arber, Robert S Ohgami
Pediatric-type follicular lymphoma and pediatric marginal zone lymphoma are two of the rarest B-cell lymphomas. These lymphomas occur predominantly in the pediatric population and show features distinct from their more common counterparts in adults: adult-type follicular lymphoma and adult-type nodal marginal zone lymphoma. Here we report a detailed whole-exome deep sequencing analysis of a cohort of pediatric-type follicular lymphomas and pediatric marginal zone lymphomas. This analysis revealed a recurrent somatic variant encoding p...
October 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Ryan Flynn, Katelyn Paz, Jing Du, Dawn K Reichenbach, Patricia A Taylor, Angela Panoskaltsis-Mortari, Ante Vulic, Leo Luznik, Kelli K P MacDonald, Geoffrey R Hill, Melanie S Nyuydzefe, Jonathan M Weiss, Wei Chen, Alissa Trzeciak, Jon S Serody, Ethan G Aguilar, William J Murphy, Ivan Maillard, David Munn, John Koreth, Corey S Cutler, Joseph H Antin, Jerome Ritz, Samuel D Waksal, Alexandra Zanin-Zhorov, Bruce R Blazar
Chronic graft-versus-host disease (cGVHD) remains a major complication following allogeneic bone marrow transplantation (BMT). The discovery of novel therapeutics is dependent on assessment in preclinical murine models of cGVHD. Rho-associated kinase 2 (ROCK2) recently was shown to be implicated in regulation of interleukin-21 (IL-21) and IL-17 secretion in mice and humans. Here, we report that the selective ROCK2 inhibitor KD025 effectively ameliorates cGVHD in multiple models: a full major histocompatibility complex (MHC) mismatch model of multiorgan system cGVHD with bronchiolitis obliterans syndrome and a minor MHC mismatch model of sclerodermatous GVHD...
April 28, 2016: Blood
Paul M Barr, Gene B Saylors, Stephen E Spurgeon, Bruce D Cheson, Daniel R Greenwald, Susan M O'Brien, Andre K D Liem, Rosemary E Mclntyre, Adarsh Joshi, Esteban Abella-Dominicis, Michael J Hawkins, Anita Reddy, Julie Di Paolo, Hank Lee, Joyce He, Jing Hu, Lyndah K Dreiling, Jonathan W Friedberg
Although agents targeting B-cell receptor signaling have provided practice-changing results in relapsed chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL), they require prolonged administration and provide incomplete responses. Given synergistic preclinical activity with phosphatidylinositol 3-kinase δ and spleen tyrosine kinase inhibition, this phase 2 study evaluated the safety and efficacy of the combination of idelalisib and entospletinib. Eligible patients with relapsed or refractory CLL or NHL underwent intrapatient dose escalation with each agent...
May 19, 2016: Blood
Kazuhiko Hayashi, Yoshiaki Katano, Masatoshi Ishigami, Akihiro Itoh, Yoshiki Hirooka, Isao Nakano, Hidemi Goto
Lamivudine (LMV) prophylaxis is effective in preventing hepatitis B virus (HBV) reactivation in patients with chronic hepatitis B undergoing chemotherapy. However, the optimal duration of LMV prophylaxis remains unclear. We report herein the case of a woman with localized follicular B-cell lymphoma who received chemotherapy with LMV prophylaxis. She achieved complete response to lymphoma, and LMV treatment was continued for 8 months after completion of chemotherapy. HBV status was still inactive. LMV was then stopped, but reactivation of hepatitis developed 1 month after cessation of LMV...
June 2009: Clinical Journal of Gastroenterology
Michael Herold, Christian W Scholz, Frank Rothmann, Carsten Hirt, Volker Lakner, Ralph Naumann
PURPOSE: The randomised, controlled OSHO#39 study showed promising results using first-line mitoxantrone, chlorambucil and prednisolone (MCP) chemotherapy plus rituximab in patients with advanced symptomatic follicular lymphoma (FL) in need of therapy. The aim of this long-term follow-up was to investigate whether clinical benefits are maintained after up to 9 years of observation. METHODS: Following the 4-year follow-up of OSHO#39, 77 FL patients who received rituximab plus MCP (R-MCP) and 52 patients who received MCP (129 patients alive and not previously censored in total) were followed for 5 additional years in this prospective, non-interventional, observational study...
September 2015: Journal of Cancer Research and Clinical Oncology
N L Berinstein, S Bhella, N M Pennell, M C Cheung, K R Imrie, D E Spaner, V Milliken, L Zhang, K Hewitt, A Boudreau, M D Reis, A Chesney, D Good, Z Ghorab, L K Hicks, E Piliotis, R Buckstein
Three sequential phase II trials were conducted with different immunotherapy approaches to enhance the outcome of autologous transplant (high-dose therapy and autologous stem cell transplantation (HDT/ASCT)) for recurrent follicular lymphoma. Seventy-three patients were enrolled from 1996 to 2009. Patients received HDT/ASCT combined with (1) interferon-α 3 MU/m(2) subcutaneously (SC) three times per week (TIW) for 2 years post-ASCT, (2) rituximab (R) 375 mg/m(2) for in vivo purging 3-5 days pre-stem cell collection and 2 × 4 weekly R at 2 and 6 months post-ASCT, respectively, or (3) three infusions of R pre-stem cell collection followed by 6× R weekly and interferon-α 3 MU/m(2) SC TIW...
May 2015: Annals of Hematology
Jelle de Wit, Tineke Jorritsma, Mateusz Makuch, Ester B M Remmerswaal, Hanny Klaasse Bos, Yuri Souwer, Jacques Neefjes, Ineke J M ten Berge, S Marieke van Ham
BACKGROUND: B cells mediate humoral immunity against pathogens but also direct CD4(+) T-cell responses. Recent plasticity studies in mice have challenged the concept of strict fate commitment during CD4(+) T-cell differentiation into distinct subsets. OBJECTIVE: We sought to elucidate the contribution of human antigen-primed B cells in CD4(+) T-cell responses that support humoral immunity. METHODS: CD4(+) T-cell differentiation by primary human B cells was investigated in in vitro cocultures by using tetanus toxoid and Salmonella species as antigen models...
April 2015: Journal of Allergy and Clinical Immunology
Luc Xerri, Emmanuel Bachy, Bettina Fabiani, Danielle Canioni, Catherine Chassagne-Clément, Peggy Dartigues-Cuilléres, Frédéric Charlotte, Nicole Brousse, Marie-Christine Rousselet, Charles Foussard, Pauline Brice, Pierre Feugier, Frank Morschhauser, Anne Sonet, Daniel Olive, Gilles Salles
Detection of MUM1+ cells in follicular lymphoma (FL) tissues was previously found to be associated with poor prognosis in a single report, whereas the usefulness of Ki-67 immunostaining remains debated. Our goal was to establish whether these markers have predictive value for patients with FL. We analyzed MUM1 and Ki-67 expression using immunohistochemistry in biopsy samples from 434 patients from the PRIMA randomized trial. The MUM1 prognostic value was then validated in a cohort of 138 patients from the FL2000 randomized trial, using the optimal cutoff value obtained from the PRIMA cohort...
October 2014: Human Pathology
Ribal Bassil, William Orent, Marta Olah, Ahmed T Kurdi, Michael Frangieh, Thomas Buttrick, Samia J Khoury, Wassim Elyaman
The transcriptional repressor B cell lymphoma 6 (BCL6) is required for the development of Th follicular cells, and it has been shown to suppress Th2 cell differentiation. We demonstrate that BCL6 is a key regulator of Th9 cell development. BCL6 expression is transiently downregulated in polarized Th9 cells, and forced expression of BCL6 in Th9 cells impairs Th9 cell differentiation. In contrast, BCL6 knockdown upregulated IL-9 production in Th9 cells. The function of BCL6 in Th9 cells is under the control of IL-2/JAK3/STAT5 signaling pathway...
July 1, 2014: Journal of Immunology: Official Journal of the American Association of Immunologists
Shingo Nakayamada, Amanda C Poholek, Kristina T Lu, Hayato Takahashi, Masanari Kato, Shigeru Iwata, Kiyoshi Hirahara, Jennifer L Cannons, Pamela L Schwartzberg, Golnaz Vahedi, Hong-Wei Sun, Yuka Kanno, John J O'Shea
CD4(+) T follicular helper cells (TFH) are critical for the formation and function of B cell responses to infection or immunization, but also play an important role in autoimmunity. The factors that contribute to the differentiation of this helper cell subset are incompletely understood, although several cytokines including IL-6, IL-21, and IL-12 can promote TFH cell formation. Yet, none of these factors, nor their downstream cognate STATs, have emerged as nonredundant, essential drivers of TFH cells. This suggests a model in which multiple factors can contribute to the phenotypic characteristics of TFH cells...
March 1, 2014: Journal of Immunology: Official Journal of the American Association of Immunologists
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