Literature DB >> 33597728

Selective elimination of immunosuppressive T cells in patients with multiple myeloma.

Mohamed H S Awwad1, Abdelrahman Mahmoud2,3, Heiko Bruns4, Hakim Echchannaoui5,6, Katharina Kriegsmann1, Raphael Lutz1, Marc S Raab1,7, Uta Bertsch1,8, Markus Munder5, Anna Jauch9, Katja Weisel10, Bettina Maier1, Niels Weinhold1, Hans Jürgen Salwender11, Volker Eckstein1, Mathias Hänel12, Roland Fenk13, Jan Dürig14, Benedikt Brors2,8, Axel Benner15, Carsten Müller-Tidow1,8,16, Hartmut Goldschmidt1,8, Michael Hundemer17.   

Abstract

Elimination of suppressive T cells may enable and enhance cancer immunotherapy. Here, we demonstrate that the cell membrane protein SLAMF7 was highly expressed on immunosuppressive CD8+CD28-CD57+ Tregs in multiple myeloma (MM). SLAMF7 expression associated with T cell exhaustion surface markers and exhaustion-related transcription factor signatures. T cells from patients with a high frequency of SLAMF7+CD8+ T cells exhibited decreased immunoreactivity towards the MART-1aa26-35*A27L antigen. A monoclonal anti-SLAMF7 antibody (elotuzumab) specifically depleted SLAMF7+CD8+ T cells in vitro and in vivo via macrophage-mediated antibody-dependent cellular phagocytosis (ADCP). Anti-SLAMF7 treatment of MM patients depleted suppressive T cells in peripheral blood. These data highlight SLAMF7 as a marker for suppressive CD8+ Treg and suggest that anti-SLAMF7 antibodies can be used to boost anti-tumoral immune responses in cancer patients.

Entities:  

Year:  2021        PMID： 33597728     DOI： 10.1038/s41375-021-01172-x

Source DB:  PubMed          Journal:  Leukemia        ISSN： 0887-6924            Impact factor:   11.528


  52 in total

1.  Molecular cloning of CS1, a novel human natural killer cell receptor belonging to the CD2 subset of the immunoglobulin superfamily.

Authors:  K S Boles; P A Mathew
Journal:  Immunogenetics       Date:  2001       Impact factor: 2.846

2.  Elotuzumab in combination with lenalidomide and dexamethasone in patients with relapsed multiple myeloma: final phase 2 results from the randomised, open-label, phase 1b-2 dose-escalation study.

Authors:  Paul G Richardson; Sundar Jagannath; Philippe Moreau; Andrzej J Jakubowiak; Marc S Raab; Thierry Facon; Ravi Vij; Darrell White; Donna E Reece; Lotfi Benboubker; Jeffrey Zonder; L Claire Tsao; Kenneth C Anderson; Eric Bleickardt; Anil K Singhal; Sagar Lonial
Journal:  Lancet Haematol       Date:  2015-11-16       Impact factor: 18.959

3.  Elotuzumab in combination with thalidomide and low-dose dexamethasone: a phase 2 single-arm safety study in patients with relapsed/refractory multiple myeloma.

Authors:  María-Victoria Mateos; Miguel Granell; Albert Oriol; Joaquin Martinez-Lopez; Joan Blade; Miguel T Hernandez; Jesus Martín; Mercedes Gironella; Mark Lynch; Eric Bleickardt; Prashni Paliwal; Anil Singhal; Jesus San-Miguel
Journal:  Br J Haematol       Date:  2016-07-19       Impact factor: 6.998

Review 4.  Multiple myeloma epidemiology and survival: A unique malignancy.

Authors:  Dickran Kazandjian
Journal:  Semin Oncol       Date:  2016-11-10       Impact factor: 4.929

Review 5.  2B4 (CD244) and CS1: novel members of the CD2 subset of the immunoglobulin superfamily molecules expressed on natural killer cells and other leukocytes.

Authors:  K S Boles; S E Stepp; M Bennett; V Kumar; P A Mathew
Journal:  Immunol Rev       Date:  2001-06       Impact factor: 12.988

6.  CS1, a potential new therapeutic antibody target for the treatment of multiple myeloma.

Authors:  Eric D Hsi; Roxanne Steinle; Balaji Balasa; Susann Szmania; Aparna Draksharapu; Benny P Shum; Mahrukh Huseni; David Powers; Amulya Nanisetti; Yin Zhang; Audie G Rice; Anne van Abbema; Melanie Wong; Gao Liu; Fenghuang Zhan; Myles Dillon; Shihao Chen; Susan Rhodes; Franklin Fuh; Naoya Tsurushita; Shankar Kumar; Vladimir Vexler; John D Shaughnessy; Bart Barlogie; Frits van Rhee; Mohamad Hussein; Daniel E H Afar; Marna B Williams
Journal:  Clin Cancer Res       Date:  2008-05-01       Impact factor: 12.531

7.  Molecular and functional characterization of a CS1 (CRACC) splice variant expressed in human NK cells that does not contain immunoreceptor tyrosine-based switch motifs.

Authors:  Jae Kyung Lee; Kent S Boles; Porunelloor A Mathew
Journal:  Eur J Immunol       Date:  2004-10       Impact factor: 5.532

8.  CS1 promotes multiple myeloma cell adhesion, clonogenic growth, and tumorigenicity via c-maf-mediated interactions with bone marrow stromal cells.

Authors:  Yu-Tzu Tai; Ender Soydan; Weihua Song; Mariateresa Fulciniti; Kihyun Kim; Fangxin Hong; Xian-Feng Li; Peter Burger; Matthew J Rumizen; Sabikun Nahar; Klaus Podar; Teru Hideshima; Nikhil C Munshi; Giovanni Tonon; Ruben D Carrasco; Daniel E H Afar; Kenneth C Anderson
Journal:  Blood       Date:  2009-02-04       Impact factor: 22.113

9.  Plasma membrane proteomics identifies biomarkers associated with MMSET overexpression in T(4;14) multiple myeloma.

Authors:  Zhigang Xie; Jayantha Gunaratne; Lip Lee Cheong; Shaw Cheng Liu; Tze Loong Koh; Gaofeng Huang; Walter P Blackstock; Wee Joo Chng
Journal:  Oncotarget       Date:  2013-07

Review 10.  Management of relapsed and refractory multiple myeloma: novel agents, antibodies, immunotherapies and beyond.

Authors:  C S Chim; S K Kumar; R Z Orlowski; G Cook; P G Richardson; M A Gertz; S Giralt; M V Mateos; X Leleu; K C Anderson
Journal:  Leukemia       Date:  2017-11-16       Impact factor: 11.528
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  2 in total

Review 1.  Promising Antigens for the New Frontier of Targeted Immunotherapy in Multiple Myeloma.

Authors:  Shih-Feng Cho; Lijie Xing; Kenneth C Anderson; Yu-Tzu Tai
Journal:  Cancers (Basel)       Date:  2021-12-06       Impact factor: 6.639

Review 2.  Therapeutics to harness the immune microenvironment in multiple myeloma.

Authors:  James J Ignatz-Hoover; James J Driscoll
Journal:  Cancer Drug Resist       Date:  2022-06-22
  2 in total

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