Article
Biophysics
Elizabeth Krieger, Rehan Qayyum, Armand Keating, Amir Toor
Summary: In unrelated donor hematopoietic cell transplant for AML, donors with higher inhibitory KIR content provide relapse protection but may come with increased transplant-related mortality, typically characterized by KIR haplotype B. Clinical trials with higher iKIR content in donors alongside strategies to reduce TRM should be considered for optimal outcomes.
BONE MARROW TRANSPLANTATION
(2021)
Article
Immunology
Sudan Tao, Yanmin He, Katherine M. Kichula, Jielin Wang, Ji He, Paul J. Norman, Faming Zhu
Summary: This study provides a detailed analysis of highly polymorphic KIR and HLA class I genes in Zhejiang Han individuals, highlighting the high frequency of KIR-A haplotypes and C1 KIR ligands in this population. The Zhejiang Han exhibit a greater diversity of inhibitory KIR compared to activating KIR, with numerous centromeric and telomeric haplotypes, as well as some haplotypes containing large-scale duplications or deletions. Additionally, a unique truncated haplotype containing only KIR2DL4 was identified, along with a high frequency of HLA-B*46:01, possibly due to selection pressure from infectious diseases.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Jean C. Digitale, Perri C. Callaway, Maureen Martin, George Nelson, Mathias Viard, John Rek, Emmanuel Arinaitwe, Grant Dorsey, Moses Kamya, Mary Carrington, Isabel Rodriguez-Barraquer, Margaret E. Feeney
Summary: The study identified a relationship between KIR and HLA genotypes and the risk of Plasmodium falciparum infection, where the presence of HLA-C2 and HLA-Bw4 increased the likelihood of infection, while HLA-C1 decreased it.
JOURNAL OF INFECTIOUS DISEASES
(2021)
Article
Multidisciplinary Sciences
Jason Pugh, Lisbeth Guethlein, Peter Parham
Summary: KIR3DL2 is an inhibitory NK cell receptor that recognizes a common epitope of human and pathogen DNA, allowing NK cells to differentiate between self and pathogen DNA and respond accordingly to activate immune responses.
Article
Immunology
Tingting Han, Juan Xie, Xiaosu Zhao, Meng Lv, Yingjun Chang, Lanping Xu, Yu Wang, Xiaohui Zhang, Kaiyan Liu, Xiao-Jun Huang, Xiang-Yu Zhao
Summary: This retrospective study evaluated the association of CMV infection with leukemia relapse and its potential mechanism. The results demonstrated that CMV infection was associated with lower survival rates, higher treatment-related mortality, and higher relapse rates. Moreover, CMV infection may promote the recovery and differentiation of NK cells.
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
(2022)
Article
Oncology
Cardozo Daniela Maira, Marangon Amanda Vansan, Guimaraes Fernando, Marques Silvia, Lieber Sofia, Delamain Marcia, Aranha Francisco Jose Penteado, Visentainer Jeane Eliete Laguila, de Souza Carmino Antonio
Summary: Through a study of 112 patients with Diffuse Large B-cell Lymphoma (DLBCL) and 222 volunteers, an association between HLA-Bw4 ligand and more advanced stages of the disease was found. It can be concluded that the polymorphism of KIR genes and the association with HLA ligands can influence the prognosis of DLBCL.
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)
Article
Immunology
Sarah Vollmers, Annabelle Lobermeyer, Annika Niehrs, Pia Fittje, Daniela Indenbirken, Jacqueline Nakel, Sanamjeet Virdi, Sebastien Brias, Timo Trenkner, Gabriel Sauer, Sven Peine, Georg M. N. Behrens, Clara Lehmann, Anja Meurer, Ramona Pauli, Nils Postel, Julia Roider, Stefan Scholten, Christoph D. Spinner, Christoph Stephan, Eva Wolf, Christoph Wyen, Laura Richert, Paul J. Norman, Juergen Sauter, Alexander H. Schmidt, Angelique Hoelzemer, Marcus Altfeld, Christian Koerner
Summary: NK cells play a crucial role in antiviral immunity, and KIR receptors regulate NK cell activity and recognition of target cells. HLA-C serves as the primary ligand for KIRs, and interactions between HLA-C and inhibitory KIR2DL receptors may contribute to HIV-1 immune evasion. This study found significant changes in the NK cell receptor repertoire in HIV-1-infected individuals and suggested that KIR/HLA-C genotypes may impact HIV-1 immune escape.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Sudan Tao, Katherine M. Kichula, Genelle F. Harrison, Ticiana Della Justina Farias, William H. Palmer, Laura Ann Leaton, Che Ghazali Norul Hajar, Zulkafli Zefarina, Hisham Atan Edinur, Faming Zhu, Paul J. Norman
Summary: The study reveals significant allelic and structural diversity of KIR and HLA class I in Malay and Malaysian Chinese populations, highlighting unique historical and genetic characteristics of both groups.
Article
Immunology
Silvia D'Amico, Valerio D'Alicandro, Mirco Compagnone, Patrizia Tempora, Giusy Guida, Paolo Romania, Valeria Lucarini, Ombretta Melaiu, Michela Falco, Mattia Algeri, Daniela Pende, Loredana Cifaldi, Doriana Fruci
Summary: The study found that the lack of ERAP1 leads to differential recognition of HLA-B*51:01 by NK cells, particularly affecting KIR3DL1-positive NK cells. This suggests that HLA-B*51:01/KIR3DL1 is one of the most sensitive combinations for ERAP1 inhibition, and individuals carrying HLA-B*51:01-like antigens may be candidates for immunotherapy based on pharmacological inhibition of ERAP1.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Cell Biology
Sofya A. Erokhina, Maria A. Streltsova, Leonid M. Kanevskiy, Maria V. Grechihina, Alexander M. Sapozhnikov, Elena I. Kovalenko
Summary: HLA-DR+ NK cells display characteristics of both NK cells and dendritic cells, and are considered significant players in the innate immune system due to their functional activities in producing cytokines, degranulation, and antigen presentation to T cells.
JOURNAL OF LEUKOCYTE BIOLOGY
(2021)
Article
Medicine, General & Internal
Vlad Andrei Cianga, Cristina Rusu, Mariana Pavel-Tanasa, Angela Dascalescu, Catalin Danaila, Sebastian Harnau, Carmen-Mariana Aanei, Petru Cianga
Summary: NK cell phenotypes and functions are diverse in AML patients, with lower NK cell counts and maturity but increased hypermature NK cells. Differences in KIR and HLA-C genotypes, as well as inhibitory receptor expressions, are observed in AML. Flow cytometry provides detailed information for evaluating NK cell numbers and phenotypes in AML patients.
FRONTIERS IN MEDICINE
(2023)
Article
Virology
Jose L. Casado, Elisa Moraga, Pilar Vizcarra, Hector Velasco, Adrian Martin-Hondarza, Johannes Haemmerle, Sandra Gomez, Carmen Quereda, Alejandro Vallejo
Summary: Infection with SARS-CoV-2 leads to increased levels of inflammatory cytokines and alterations in the distribution and phenotype of NK cells, which may enhance the impairment of the crucial innate defense during COVID-19 infection.
Article
Immunology
David Tomaz, Pedro Matos Pereira, Nadia Guerra, Julian Dyson, Keith Gould, Ricardo Henriques
Summary: NK cell inhibition and activation rely on the nanoscale colocalization of their receptors. NKG2D and Ly49A integrate signals at the immune synapse based on their relative positioning, which is affected by the size of NK cell ligand-receptor pairs.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Minh-Trang Thi Phan, Jinho Kim, Seung Kwon Koh, Yuree Lim, Hongbi Yu, Mijeong Lee, Jong-Min Lee, Eun-Suk Kang, Hyun-Young Kim, Sang-Ki Kim, Ilwoong Hwang, Duck Cho
Summary: This study presents an effective method for expanding adaptive NK cells using genetically modified feeder cells, which can generate a large number of NK cells with high cytotoxicity and interferon-gamma production in vitro, providing a high yield of applicable cells for cancer cell therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Marco Greppi, Valentina Obino, Rayan Goda, Federico Rebaudi, Simona Carlomagno, Mariella Della Chiesa, Simona Sivori, Gianluca Ubezio, Vanessa Agostini, Alessandra Bo, Silvia Pesce, Emanuela Marcenaro
Summary: This study is the first to report PD-1 expression on CB derived NK cells and its features in perinatal conditions. These data may prove important in selecting the most suitable CB derived NK cell population for the development of different immunotherapeutic treatments.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Dentistry, Oral Surgery & Medicine
Karin Garming Legert, Olle Ringden, Mats Remberger, Johan Torlen, Jonas Mattsson, Goran Dahllof
Summary: The study found that using tacrolimus plus sirolimus as a prophylaxis for graft-versus-host disease following haematopoietic stem cell transplantation did not increase the incidence or severity of oral mucositis, nor did it prolong the healing time compared to cyclosporine plus methotrexate.
Article
Hematology
Olle Ringden, Mats Remberger, Johan Torlen, Sigrun Finnbogadottir, Britt-Marie Svahn, Behnam Sadeghi
Summary: Patients treated at home post-HCT showed decreased cytokine levels, improved survival, and lower rates of III-IV acute GVHD compared to patients treated in the hospital. Various factors such as GVHD grade, donor type, conditioning regimen, and graft source influenced cytokine levels and outcomes.
INTERNATIONAL JOURNAL OF HEMATOLOGY
(2021)
Article
Biophysics
Mary-Elizabeth Percival, Hai-Lin Wang, Mei-Jie Zhang, Wael Saber, Marcos de Lima, Mark Litzow, Partow Kebriaei, Hisham Abdel-Azim, Kehinde Adekola, Mahmoud Aljurf, Ulrike Bacher, Sherif M. Badawy, Amer Beitinjaneh, Nelli Bejanyan, Vijaya Bhatt, Michael Byrne, Jean-Yves Cahn, Paul Castillo, Nelson Chao, Saurabh Chhabra, Edward Copelan, Corey Cutler, Zachariah DeFilipp, Ajoy Dias, Miguel Angel Diaz, Elihu Estey, Nosha Farhadfar, Haydar A. Frangoul, Cesar O. Freytes, Robert Peter Gale, Siddhartha Ganguly, Lohith Gowda, Michael Grunwald, Nasheed Hossain, Rammurti T. Kamble, Christopher G. Kanakry, Ankit Kansagra, Mohamed A. Kharfan-Dabaja, Maxwell Krem, Hillard M. Lazarus, Jong Wook Lee, Jane L. Liesveld, Richard Lin, Hongtao Liu, Joseph McGuirk, Reinhold Munker, Hemant S. Murthy, Sunita Nathan, Taiga Nishihori, Richard F. Olsson, Neil Palmisiano, Jakob R. Passweg, Tim Prestidge, Olov Ringden, David A. Rizzieri, Witold B. Rybka, Mary Lynn Savoie, Kirk R. Schultz, Sachiko Seo, Akshay Sharma, Melhem Solh, Roger Strair, Marjolein van der Poel, Leo F. Verdonck, Jean A. Yared, Daniel Weisdorf, Brenda M. Sandmaier
Summary: The study found that in AML patients, those in CRi had increased risk of death compared to those in CR, along with higher non-relapse mortality, shorter disease-free survival, and increased relapse. Detectable MRD was associated with shorter overall survival, shorter disease-free survival, higher non-relapse mortality, and increased relapse. The detrimental effects of CRi and MRD were independent.
BONE MARROW TRANSPLANTATION
(2021)
Article
Oncology
Neema P. Mayor, Tao Wang, Stephanie J. Lee, Michelle Kuxhausen, Cynthia Vierra-Green, Dominic J. Barker, Jeffrey Auletta, Vijaya R. Bhatt, Shahinaz M. Gadalla, Loren Gragert, Yoshihiro Inamoto, Gerald P. Morris, Sophie Paczesny, Ran Reshef, Olle Ringden, Bronwen E. Shaw, Peter Shaw, Stephen R. Spellman, Steven G. E. Marsh
Summary: This study found that UHR HLA matching may not increase overall survival probability, but it does reduce the risk of aGVHD and in certain subsets, transplant-related mortality. Matching at the UHR level warrants consideration when choosing between multiple 10 out of 10 HLA-matched donors.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Article
Multidisciplinary Sciences
Anne-Sophie Chretien, Raynier Devillier, Samuel Granjeaud, Charlotte Cordier, Clemence Demerle, Nassim Salem, Julia Wlosik, Florence Orlanducci, Laurent Gorvel, Stephane Fattori, Marie-Anne Hospital, Jihane Pakradouni, Emilie Gregori, Magali Paul, Philippe Rochigneux, Thomas Pagliardini, Mathieu Morey, Cyril Fauriat, Nicolas Dulphy, Antoine Toubert, Herve Luche, Marie Malissen, Didier Blaise, Jacques A. Nunes, Norbert Vey, Daniel Olive
Summary: The accumulation of CD56(-)CD16(+) unconventional NK cells in patients with acute myeloid leukemia may be a consequence of immune escape from innate immunity during AML progression.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Oncology
Raynier Devillier, Boris Calmels, Sophie Guia, Mohammed Taha, Cyril Fauriat, Bechara Mfarrej, Geoffroy Venton, Eric Vivier, Daniel Olive, Christian Chabannon, Didier Blaise, Sophie Ugolini
Summary: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective curative option for high-risk hematologic malignancies, but disease recurrence remains a critical issue. NK cell-based immunotherapies offer a promising approach to enhance anti-tumor effects without triggering graft-versus-host disease. This clinical trial demonstrates the safety and potential efficacy of prophylactic donor-derived IL-2 activated NK cell infusion after allo-HSCT for patients with hematologic malignancies.
Article
Hematology
Matthew J. Wieduwilt, Leland Metheny, Mei-Jie Zhang, Hai-Lin Wang, Noel Estrada-Merly, David Marks, A. Samer Al-Homsi, Lori Muffly, Nelson Chao, David Rizzieri, Robert Peter Gale, Shahinaz M. Gadalla, Mitchell Cairo, Alberto Mussetti, Steven Gore, Vijaya Raj Bhatt, Sagar S. Patel, Fotios Michelis, Yoshihiro Inamoto, Sherif M. Badawy, Edward Copelan, Neil Palmisiano, Mohamed A. Kharfan-Dabaja, Hillard M. Lazarus, Siddhartha Ganguly, Christopher Bredeson, Miguel Angel Diaz Perez, Ryan Cassaday, Bipin N. Savani, Karen Ballen, Rodrigo Martino, Baldeep Wirk, Ulrike Bacher, Mahmoud Aljurf, Asad Bashey, Hemant S. Murthy, Jean A. Yared, Ibrahim Aldoss, Nosha Farhadfar, Hongtao Liu, Hisham Abdel-Azim, Edmund K. Waller, Melhem Solh, Matthew D. Seftel, Marjolein van der Poel, Michael R. Grunwald, Jane L. Liesveld, Rammurti T. Kamble, Joseph McGuirk, Reinhold Munker, Jean-Yves Cahn, Jong Wook Lee, Cesar O. Freytes, Maxwell M. Krem, Lena E. Winestone, Usama Gergis, Sunita Nathan, Richard F. Olsson, Leo F. Verdonck, Akshay Sharma, Olle Ringden, Brian D. Friend, Jan Cerny, Hannah Choe, Saurabh Chhabra, Taiga Nishihori, Sachiko Seo, Biju George, Lee Ann Baxter-Lowe, Gerhard C. Hildebrandt, Marcos de Lima, Mark Litzow, Partow Kebriaei, Christopher S. Hourigan, Muhammad Bilal Abid, Daniel J. Weisdorf, Wael Saber
Summary: This study compared the outcomes of haploidentical hematopoietic cell transplantation (HCT) using posttransplant cyclophosphamide (PTCy) with other HCT approaches for acute lymphoblastic leukemia (ALL) patients. The results showed that haploidentical HCT using PTCy had similar overall survival (OS) but lower incidence of chronic graft-versus-host disease (cGVHD) compared to traditional matched sibling and unrelated donor HCT methods, making it a preferred alternative donor option for ALL patients in complete remission.
Article
Immunology
Berna Bou-Tayeh, Vladimir Laletin, Nassim Salem, Sylvaine Just-Landi, Joanna Fares, Raphael Leblanc, Marielle Balzano, Yann M. Kerdiles, Ghislain Bidaut, Olivier Herault, Daniel Olive, Michel Aurrand-Lions, Thierry Walzer, Jacques A. Nunes, Cyril Fauriat
Summary: NK cells in AML patients exhibit defects in maturation and function due to chronic cytokine activation, particularly IL-15/mTOR signaling, leading to metabolic and functional exhaustion.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Olle Ringden, Guido Moll, Britt Gustafsson, Behnam Sadeghi
Summary: This article summarizes the authors' more than 20 years of scientific experience in the clinical use of MSCs and DSCs in different clinical settings. MSCs and DSCs have significant effects on the immune system and coagulation, and show potential clinical efficacy in conditions such as acute GvHD, ARDS, and hemorrhages.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell & Tissue Engineering
Behnam Sadeghi, Myrese Witkamp, Dominik Schefberger, Anna Arbman, Olle Ringden
Summary: Human placenta-derived decidua stromal cells (DSCs) have been used in clinical trials for the treatment of acute inflammatory diseases, but the mechanisms of action and interaction with other immune cells require further exploration.
Article
Immunology
Behnam Sadeghi, Olle Ringden, Britt Gustafsson, Markus Castegren
Summary: Acute respiratory distress syndrome (ARDS) is a life-threatening lung disease. Mesenchymal stromal cells (MSCs) have been evaluated as a therapy for ARDS, and the use of MSCs for ARDS induced by Covid-19 has shown positive results. Clinical and experimental studies have demonstrated the effectiveness of MSCs in treating sepsis and ARDS.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Medicine, Research & Experimental
Raphael Leblanc, Rania Ghossoub, Armelle Goubard, Remy Castellano, Joanna Fares, Luc Camoin, Stephane Audebert, Marielle Balzano, Berna Bou-Tayeh, Cyril Fauriat, Norbert Vey, Sylvain Garciaz, Jean-Paul Borg, Yves Collette, Michel Aurrand-Lions, Guido David, Pascale Zimmermann
Summary: This study reveals a vicious signaling loop potentially at the heart of AML-stroma crosstalk and unexpected tumor-suppressive effects of syntenin that need to be considered during systemic targeting of syntenin in cancer therapy.
EMBO MOLECULAR MEDICINE
(2023)
Article
Hematology
Alvaro Haroun-Izquierdo, Pilar M. Lanuza, Aline Pfefferle, Herman Netskar, Eivind H. Ask, Johan Torlen, Andreas Bjorklund, Ebba Sohlberg, Karl -Johan Malmberg
Summary: Sirolimus, an inhibitor of mTOR, shows potential as a component of GVHD prophylaxis regimens in HSCT, but detailed immunologic studies are lacking. This study evaluated the effect of sirolimus on immune reconstitution using longitudinal patient samples. Sirolimus inhibited naive cell suppression and NK cell reconstitution, leading to impaired proliferation and functional responses.
TRANSPLANTATION AND CELLULAR THERAPY
(2023)
Article
Hematology
Rima M. Salibaaw, Amin M. Alousia, Joseph Pidala, Mukta Arora, Stephen R. Spellman, Michael T. Hemmer, Tao Wang, Camille Abboudg, Sairah Ahmed, Joseph H. Antin, Amer Beitinjanehi, David K. Buchbinder, Michael Byrne, Jean-Yves Cahn, Hannah Choen, Rabi Hanna, Peiman HemattiP, Rammurti T. Kamble, Carrie L. Kitkor, Mary Laughlin, Lazaros Lekakis, Margaret L. MacMillan, Rodrigo Martino, Parinda A. Mehta, Taiga Nishihori, Sagar S. Patel, Miguel-Angel Perales, Hemalatha G. Rangarajan, Olov Ringden, Joseph Rosenthal, Bipin N. Savani, Kirk R. Schultz, Sachiko Seo, Takanori Teshimaag, Marjolein van der Poela, Leo F. Verdonck, Daniel Weisdorf, Baldeep Wirk, Jean A. Yared, Jeffrey Schriber, Richard E. Champlin, Stefan O. Ciurea
Summary: This retrospective registry study compared the distribution, severity, and outcomes of graft-versus-host disease (GvHD) in patients receiving haploidentical (Haplo) transplantation with post-transplantation cyclophosphamide (PTCy) prophylaxis and HLA-matched unrelated donor transplantation with conventional prophylaxis. The study found that Haplo/PTCy transplantation was associated with reduced rates of severe acute GvHD and chronic GvHD, particularly in the gastrointestinal (GI) tract.
TRANSPLANTATION AND CELLULAR THERAPY
(2022)
Article
Hematology
Leland Metheny, Natalie S. Callander, Aric C. Hall, Mei-Jei Zhang, Khalid Bo-Subait, Hai-Lin Wang, Vaibhav Agrawal, A. Samer Al-Homsi, Amer Assal, Ulrike Bacher, Amer Beitinjaneh, Nelli Bejanyan, Vijaya Raj Bhatt, Chris Bredeson, Michael Byrne, Mitchell Cairo, Jan Cerny, Zachariah DeFilipp, Miguel Angel Diaz Perez, Esar O. Freytes, Siddhartha Ganguly, Michael R. Grunwald, Shahrukh Hashmi, Gerhard C. Hildebrandt, Yoshihiro Inamoto, Christopher G. Kanakry, Mohamed A. Kharfan-Dabaja, Hillard M. Lazarus, Jong Wook Lee, Sunita Nathan, Taiga Nishihori, Richard F. Olsson, Olov Ringden, David Rizzieri, Bipin N. Savani, Mary Lynn Savoie, Sachiko Seo, Marjolein van der Poel, Leo F. Verdonck, John L. Wagner, Jean A. Yared, Christopher S. Hourigan, Partow Kebriaei, Mark Litzow, Brenda M. Sandmaier, Wael Saber, Daniel Weisdorf, Marcos de Lima
Summary: The prognosis for patients with therapy-related myeloid neoplasm, including myelodysplastic syndrome (t-MDS) and acute myelogenous leukemia (t-AML), is poor. Although modern supportive care and conditioning regimens have improved outcomes, the major cause of treatment failure remains relapse. Caution is advised when recommending allogeneic hematopoietic cell transplantation, and more effective antineoplastic approaches are needed.
TRANSPLANTATION AND CELLULAR THERAPY
(2021)