Augmented expression of programmed death‐1 in both neoplastic and non‐neoplastic CD4⁺ T‐cells in adult T‐cell leukemia/lymphoma

Abstract

Adult T-cell leukemia/lymphoma (ATL) is a CD4 1 CD25 1 T-cell malignancy infected with human T-cell leukemia virus type-I (HTLV-I). HTLV-I infection causes the T-cell dysfunction, which contributes to the immunodeficient state of the patients. Programmed death-1 (PD-1) can negatively regulate T-cell response, when its ligand, PD-L1 or PD-L2 mainly expressed on antigen presenting cells, binds to this B7 family receptor. We investigated whether PD-1 is expressed on CD4 1 neoplastic (and/or non-neoplastic) cells or CD8 1 cytotoxic cells in peripheral blood mononuclear cells from 11 patients with ATL. By flow cytometry, we found that the levels of PD-1 expression on both CD4 1 CD25 1 and CD4 1 CD25 2 T-cell populations were increased in ATL patients compared to normal healthy volunteers, while PD-1 levels on CD8 1 T-cells were comparable between the patients and normal subjects. In stimulation with anti-CD3 antibody, the proliferation of PD-1-expressing T-cells from ATL patients was weak when compared to that of PD-1-nonexpressing normal T-cells. In addition to PD-1, PD-L1 was coexpressed on ATL cells in some patients, and PD-L1 expression was enhanced by stimulation with anti-CD3 antibody. Finally, the production of cytokines such as TNF-a by ATL cells was restored by blockade of PD-1/PD-L1 interaction. These findings suggest that CD4 1 T-cells are the main PD-1-expressing cells rather than CD8 1 T-cells in ATL patients, and both neoplastic and normal CD4 1 cells are exhausted as a result of PD-1 expression, and additionally PD-L1 expression on the neoplastic cell. ' 2007 Wiley-Liss, Inc.

PD-1/PD-L1 expression in human T-cell leukemia virus type 1 carriers and adult T-cell leukemia/lymphoma patients

“…Samples from all five patients who express high PD-L1 on CD4 þ CD25 þ cells (410%) were collected at least 12 months after diagnosis. Shimauchi et al 42 also reported that CD4 þ CD25 þ tumor cells expressed a low but discernible level of PD-L1 in only one of four cases. This and our data are in contrast with an earlier study that assessed PD-L1 expression in 30 heterogenous acute leukemia patients and found that 57% of patients expressed PD-L1 at diagnosis on leukemic cells.…”

The PD-1/PD-L1 axis contributes to T-cell dysfunction in chronic lymphocytic leukemia

“…36 In the neoplastic context, PD-1 is reported as expressed by tumor infiltrating, as well as circulating, T lymphocytes in Hodgkin's and non-Hodgkin's lymphomas and in adult T-cell leukemia. 27,37,38 Furthermore, PD-1 + helper T cells were identified as an independent prognostic risk factor for decreased overall survival in follicular lymphoma. 39 Expression of PD-1 on the neoplastic counterpart was reported in a limited number of diffuse large B-cell lymphomas and in a more significant number of small lymphocytic lymphomas.…”

Tumor cell expression of programmed cell death‐1 ligand 1 is a prognostic factor for malignant melanoma

“…The expression of PD-L1 in tumors has been reported in melanoma 19,20 ; in cancers of the lung, 19 breast, 21 ovary, 22 kidney, 23 pancreas, 24 esophageus, 25 and bladder 26 ; and even in adult T-cell leukemia/lymphoma. 27 In addition, the involvement of PD-L1 has been demonstrated in the protection of cancer cells from cell lysis by activated T lymphocytes. 28 However, the expression of PD-L1 on melanoma cells in relation to tumor cell behavior and prognosis remains to be elucidated.…”