Nectin-2 Expression on Malignant Plasma Cells Is Associated with Better Response to TIGIT Blockade in Multiple Myeloma.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Ester LozanoCarlos Fernández de Larrea

Abstract

T-cell immunoreceptor with Ig and ITIM domain (TIGIT) blockade could represent an alternative therapeutic option to release the immune response in patients with multiple myeloma. Here we analyzed the expression of TIGIT and its ligands poliovirus receptor (PVR) and nectin-2 in the bone marrow (BM) of patients with monoclonal gammopathies and the efficacy of TIGIT blockade activating antimyeloma immunity. Expression levels of TIGIT and its ligands were characterized by flow cytometry and ELISA. TIGIT blockade was analyzed in in vitro functional assays with peripheral T cells. BM cells were studied with NanoString technology, real-time PCR, and ex vivo patient BM cell models. TIGIT and its ligands are highly expressed in the BM of patients with multiple myeloma, suggesting that may play a role in restraining immune activation. TIGIT blockade depleted FoxP3+ Tregs while increasing proliferation of IFNγ-producing CD4+ T cells from patients with multiple myeloma. PVR ligation inhibited CD8+ T-cell signaling and cell proliferation which could be overcome with anti-TIGIT mAb. However, BM cells showed a remarkable heterogeneity in immune signature. Accordingly, functional ex vivo BM assays revealed that only some patients respond to ch...Continue Reading

References

Jun 6, 2003·British Journal of Haematology·Britta MaeckerJoachim L Schultze
Aug 13, 2003·The Journal of Experimental Medicine·Cristina BottinoAlessandro Moretta
Sep 10, 2005·Blood·Rao H PrabhalaNikhil C Munshi
Aug 16, 2006·The New England Journal of Medicine·Arlene H Sharpe, Abul K Abbas
Jun 22, 2007·The New England Journal of Medicine·Robert A KyleS Vincent Rajkumar
Oct 10, 2009·Proceedings of the National Academy of Sciences of the United States of America·Noa StanietskyOfer Mandelboim
Dec 23, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Joan BladéRobert A Kyle
Jun 8, 2010·The New England Journal of Medicine·F Stephen HodiWalter J Urba
Oct 15, 2010·Annals of Oncology : Official Journal of the European Society for Medical Oncology·J BladéL Rosiñol
Jan 5, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nicole JollerVijay K Kuchroo
Mar 19, 2011·European Journal of Immunology·Steven D LevinKatherine E Lewis
Feb 1, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Joan BladéLaura Rosiñol
Mar 17, 2012·Proceedings of the National Academy of Sciences of the United States of America·Katharina F StengelJane L Grogan
Mar 20, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ester LozanoDavid A Hafler
Aug 28, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ester LozanoDavid A Hafler
Oct 25, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Scott J AntoniaPaolo A Ascierto
Jan 15, 2015·Blood·Joan BladéCarlos Fernández de Larrea
Sep 29, 2015·The Journal of Clinical Investigation·Sema KurtulusAna C Anderson
Oct 16, 2015·Cancer Immunology Research·David J ChungJames W Young
Feb 28, 2016·The Oncologist·Jo CaersMonika Engelhardt
Nov 3, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Stephen J BlakeMark J Smyth
Mar 5, 2017·Immunological Reviews·William C DougallAna C Anderson
May 19, 2017·The Journal of Biological Chemistry·Felix A DeussRichard Berry
Sep 14, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Matthew J PiankoAlexander M Lesokhin
Mar 4, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Karen O DixonNicole Joller
Mar 14, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ester LozanoCarlos Fernández de Larrea
Oct 3, 2018·Cellular & Molecular Immunology·Paola Kučan BrlićStipan Jonjić
Jan 20, 2019·Cancer Immunology Research·Sarah WhelanSpencer C Liang

❮ Previous
Next ❯

Citations

Aug 10, 2021·Frontiers in Immunology·Zhouhong GeJaap Kwekkeboom
Aug 27, 2021·Journal of Experimental & Clinical Cancer Research : CR·Baokang WuYu Tian
Aug 27, 2021·Journal for Immunotherapy of Cancer·Mireia BachillerBeatriz Martin-Antonio
Aug 28, 2021·Frontiers in Immunology·Mikel Etxebeste-MitxeltorenaBeatriz Martín-Antonio

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Genomics (Keystone)

Cancer genomics approaches employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest research using such technologies in this feed.