Title |
Expression of LAG-3 by tumor-infiltrating lymphocytes is coincident with the suppression of latent membrane antigen–specific CD8+ T-cell function in Hodgkin lymphoma patients
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Published in |
Blood, June 2006
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DOI | 10.1182/blood-2006-04-015164 |
Pubmed ID | |
Authors |
Maher K. Gandhi, Eleanore Lambley, Jaikumar Duraiswamy, Ujjwal Dua, Corey Smith, Suzanne Elliott, Devinder Gill, Paula Marlton, John Seymour, Rajiv Khanna |
Abstract |
In Hodgkin lymphoma (HL), the malignant Hodgkin Reed-Sternberg (HRS) cells constitute only 0.5% of 10% of the diseased tissue. The surrounding cellular infiltrate is enriched with T cells that are hypothesized to modulate antitumor immunity. We show that a marker of regulatory T cells, LAG-3, is strongly expressed on infiltrating lymphocytes present in proximity to HRS cells. Circulating regulatory T cells (CD4+ CD25hi CD45 ROhi, CD4+ CTLA4hi, and CD4+ LAG-3hi were elevated in HL patients with active disease when compared with remission. Longitudinal profiling of EBV-specific CD8+ T-cell responses in 94 HL patients revealed a selective loss of interferon-gamma expression by CD8+ T cells specific for latent membrane proteins 1 and 2 (LMP1/2), irrespective of EBV tissue status. Intratumoral LAG-3 expression was associated with EBV tissue positivity, whereas FOXP3 was linked with neither LAG-3 nor EBV tissue status. The level of LAG-3 and FOXP3 expression on the tumor-infiltrating lymphocytes was coincident with impairment of LMP1/2-specific T-cell function. In vitro pre-exposure of peripheral blood mononuclear cells to HRS cell line supernatant significantly increased the expansion of regulatory T cells and suppressed LMP-specific T-cell responses. Deletion of CD4+ LAG-3+ T cells enhanced LMP-specific reactivity. These findings indicate a pivotal role for regulatory T cells and LAG-3 in the suppression of EBV-specific cell-mediated immunity in HL. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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United States | 2 | 2% |
Japan | 1 | <1% |
Spain | 1 | <1% |
France | 1 | <1% |
Unknown | 128 | 96% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 36 | 27% |
Student > Ph. D. Student | 22 | 17% |
Student > Master | 16 | 12% |
Other | 13 | 10% |
Student > Bachelor | 10 | 8% |
Other | 19 | 14% |
Unknown | 17 | 13% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 42 | 32% |
Agricultural and Biological Sciences | 34 | 26% |
Immunology and Microbiology | 18 | 14% |
Biochemistry, Genetics and Molecular Biology | 8 | 6% |
Pharmacology, Toxicology and Pharmaceutical Science | 3 | 2% |
Other | 6 | 5% |
Unknown | 22 | 17% |