PD1 is expressed on exhausted T cells as well as virus specific memory CD8+ T cells in the bone marrow of myeloma patients

Oncotarget
Anne-Marit SponaasAnders Sundan

Abstract

Characterization of CD8+ T cells in the tumor microenvironment (TME) is important to predict responses to checkpoint therapy. The TME in multiple myeloma is the bone marrow, which also is an immune organ where immune responses are generated and memory cells stored. The presence of T cells with other specificities than the tumor in the bone marrow may affect the search for biomarkers to predict responses to immunotherapy in myeloma. Here, we found similar proportions of PD1+ CD8+ T cells and similar levels of PD1 expression on CD8+ T cells in the bone marrow of myeloma patients and healthy controls. PD1 expression on CD8+ T cells did not correlate with tumor load suggesting that at least some of the PD1+ CD8+ T cells were specific for non-myeloma antigens. Indeed, PD1+ EBV-specific CD8+ T cells were detected it the bone marrow of patients. Terminal effectors (Teff), effector memory (Tem) and central memory (Tcm) cells as well as exhausted T cells were all found in the myeloma bone marrow. However, myeloma patients had more terminal effectors and fewer memory cells than healthy controls suggesting that the tumor generate an immune response against myeloma cells in the bone marrow. The presence of CD8 EOMEShigh Tbetlow T cells wit...Continue Reading

References

Nov 26, 2003·The Journal of Experimental Medicine·Madhav V DhodapkarMatthew D Geller
Sep 13, 2005·Nature Immunology·Lois L CavanaghUlrich H von Andrian
Jan 5, 2008·Annual Review of Immunology·Mary E KeirArlene H Sharpe
Jun 4, 2010·Expert Review of Vaccines·Liubov ZaritskayaAnatoli M Malyguine
Mar 9, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jaikumar DuraiswamyRafi Ahmed
Nov 22, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Evan J LipsonSuzanne L Topalian
Apr 24, 2013·Proceedings of the National Academy of Sciences of the United States of America·Fang WeiJames L Riley
Oct 12, 2013·Nature Reviews. Immunology·Vanja LazarevicGraham M Lord
Jun 14, 2014·Proceedings of the National Academy of Sciences of the United States of America·Anna OkhrimenkoJun Dong
Dec 3, 2014·The Lancet Oncology·S Vincent RajkumarJesus F San Miguel
Dec 24, 2014·Nature Reviews. Immunology·Linh T Nguyen, Pamela S Ohashi
May 17, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Güllü GörgünKenneth C Anderson
Oct 16, 2015·Cancer Immunology Research·David J ChungJames W Young
Apr 16, 2016·Nature Reviews. Cancer·Suzanne L TopalianDrew M Pardoll
Jun 9, 2016·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Alexander M LesokhinJohn Timmerman
Sep 30, 2016·Oncotarget·Katarzyna BaranowskaAnders Sundan
Oct 11, 2016·The New England Journal of Medicine·Martin ReckUNKNOWN KEYNOTE-024 Investigators
Nov 5, 2016·Journal of Hematology & Oncology·Claudia Zelle-RieserKarin Jöhrer
Jan 14, 2017·Haematologica·Paula Rodríguez-OteroJesús F San Miguel
Jan 20, 2017·Nature·Daniel S Chen, Ira Mellman
Mar 25, 2017·Nature Reviews. Cancer·Philip GotwalsGlenn Dranoff
Apr 12, 2017·Nature·Alexander C HuangE John Wherry

❮ Previous
Next ❯

Citations

Apr 6, 2019·Anti-cancer Agents in Medicinal Chemistry·Vladimir S RogovskiiNikolai L Shimanovskii
Jan 9, 2019·Frontiers in Immunology·Jing LiChen Dong
Aug 3, 2019·Cancer Immunology Research·Alexander M LesokhinAshraf Z Badros
Mar 30, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Nouf AlrasheedKwee L Yong
Mar 9, 2021·Frontiers in Immunology·Anne Marit SponaasTherese Standal
Mar 16, 2021·Frontiers in Immunology·Samuel S McCachrenMadhav V Dhodapkar
Mar 25, 2021·Technology in Cancer Research & Treatment·Yu ZhangCheng-Hao Jin
Jun 3, 2021·International Journal of Molecular Sciences·James D WestAnandharajan Rathinasabapathy

❮ Previous
Next ❯

Methods Mentioned

BETA
Fluorescence
ISS
Flow cytometry
dissection
PMA

Software Mentioned

FACS Diva
Tbet

Related Concepts

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.