Retinoic acid induction of CD1d expression primes chronic lymphocytic leukemia B cells for killing by CD8+ invariant natural killer T cells.
Clin Immunol
; 183: 91-98, 2017 10.
Article
in En
| MEDLINE
| ID: mdl-28780376
ABSTRACT
Invariant natural killer T (iNKT) cells are cytotoxic T cells that respond to glycolipid antigens presented by CD1d. Therapeutic activation of iNKT cells with α-galactosylceramide (α-GalCer) can prevent and reverse tumor growth in mice and clinical trials involving α-GalCer-stimulated iNKT cells are ongoing in humans. B cells express CD1d, however, we show that CD1d expression is reduced on B cells from patients with chronic lymphocytic leukemia (CLL). B cells from CLL patients pulsed with α-GalCer failed to stimulate cytolytic degranulation by iNKT cell lines, but could present the more potent glycolipid analogue, 7DW8-5. Retinoic acid receptor-α (RAR-α) agonists induced CD1d expression by CLL B cells, restoring their ability to present α-GalCer to CD8α+ iNKT cells, resulting in cytolytic degranulation. Thus, RAR-α agonists can augment the anti-tumor activities of iNKT cells against CLL cells in vitro. Their inclusion in iNKT cell-based therapies may benefit patients with CLL.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Tetrahydronaphthalenes
/
Tretinoin
/
Benzoates
/
B-Lymphocytes
/
Antigen Presentation
/
CD8-Positive T-Lymphocytes
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Natural Killer T-Cells
/
Antigens, CD1d
/
Galactosylceramides
/
Antineoplastic Agents
Limits:
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Clin Immunol
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2017
Document type:
Article
Affiliation country:
Ireland