CD86+ or HLA-G+ can be transferred via trogocytosis from myeloma cells to T cells and are associated with poor prognosis.
The transfer of membrane proteins between cells during contact, known as trogocytosis, can create novel cells with a unique phenotype and altered function. We demonstrate that trogocytosis is more common in multiple myeloma (MM) than chronic lymphocytic leukemia and Waldenstrom macroglobulinaemia; that T cells are more probable to be recipients than B or natural killer cells; that trogocytosis occurs independently of either the T-cell receptor or HLA compatibility; and that after trogocytosis, T cells with acquired antigens can become novel regulators of T-cell proliferation. We screened 168 patients with MM and found that CD86 and human leukocyte antigen G (HLA-G) were antigens commonly acquired by T cells from malignant plasma cells. CD3+ CD86acq+ and CD3+ HLA-Gacq+ cells were more prevalent in bone marrow than peripheral blood samples. The presence of either CD86 or HLA-G on malignant plasma cells was associated with a poor prognosis. CD38++ side population cells expressed HLA-G, suggesting that these putative myeloma stem cells could generate immune tolerance. HLA-G+ T cells had a regulatory potency similar to natural Tregs, thus providing another novel mechanism for MM to avoid effective immune surveillance.
Institute of Haematology, Royal Prince Alfred Hospital, Sydney, Australia. ross.brown@sswahs.nsw.gov.au
Ross
R
Brown
Karieshma
K
Kabani
James
J
Favaloro
Shihong
S
Yang
P Joy
PJ
Ho
John
J
Gibson
Phillip
P
Fromm
Hayley
H
Suen
Narelle
N
Woodland
Najah
N
Nassif
Derek
D
Hart
Douglas
D
Joshua
D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D051940:B7-2 Antigen / Q000276:immunology*; D015415:Biomarkers / Q000032:analysis; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D059951:HLA-G Antigens / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology / Q000378:metabolism* / Q000401:mortality; D009101:Multiple Myeloma / Q000276:immunology / Q000378:metabolism* / Q000401:mortality; D009928:Organ Specificity; D010950:Plasma Cells / Q000276:immunology* / Q000378:metabolism; D011379:Prognosis; D021381:Protein Transport / Q000276:immunology; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D008258:Waldenstrom Macroglobulinemia / Q000276:immunology / Q000378:metabolism* / Q000401:mortality
D051940:B7-2 Antigen; D015415:Biomarkers; D059951:HLA-G Antigens