Circulating Natural Killer Lymphocytes Are Potential Cytotoxic Effectors Against Autologous Malignant Cells in Sezary Syndrome Patients

Abstract

Patients with advanced cutaneous T cell lymphoma (CTCL) exhibit profound defects in cell-mediated immunity. Although it has been suggested that Sezary syndrome (SS) patients have a decreased natural killer (NK) lymphocyte activity, nothing has been reported concerning the sensitivity of Sezary cells to NK lymphocyte-mediated cytotoxicity. Peripheral blood NK cells from healthy donors were tested against Sezary tumoral cell lines as well as against freshly isolated Sezary cells. Further, we studied their ability to exhibit antibody -dependent cell-mediated cytotoxicity using either the murine anti-CD158k/KIR3DL2 monoclonal antibody (moAb) AZ158 that specifically recognizes Sezary cells, or the anti-CD52 monoclonal antibody alemtuzumab. The results show that Sezary cell lines are susceptible to NK lymphocyte lysis. More importantly, we found that freshly isolated malignant cells are killed either by IL-2 activated allogeneic NK lymphocytes or when the tumor lymphocyte targets are incubated with an anti-MHC class I F(ab)'2 antibody. Further, anti-KIR3DL2 and anti-CD52 moAb can enhance the NK lysis. Finally, we report that NK lymphocytes isolated from SS patients are potentially cytotoxic lymphocytes against autologous malignant Sezary cells. These findings indicate that antitumor-mediated NK lymphocyte cytotoxic activity can be triggered in patients with CTCL and raise the possibility of developing novel therapeutic strategies by stimulating their innate immunity.

Expression of T-plastin, FoxP3 and other tumor-associated markers by leukemic T-cells of cutaneous T-cell lymphoma

“…However, it remained unclear whether this was due to a decrease of the NK cell numbers, impairment of their cytotoxic function, or both. Recent studies of SS have confirmed a quantitative decrease of NK cells, but also indicate that NK cells are capable of lyzing autologous neoplastic cells as well neoplastic cell lines derived from SS [30,31].…”

Highly cytotoxic natural killer cells are associated with poor prognosis in patients with cutaneous T-cell lymphoma

“…41 It is also possible that the process of NK-cell recognition of malignant CD4 1 T cells is altered in CTCL patients. Previous studies by Bouaziz et al 15 suggest that NK cells are potentially able to be activated to kill autologous CTCL cells, which suggests that malignant CD4…”

“…Previous groups have reported that NK cells from SS patients are capable of responding to activation ex vivo, indicating the potential for development of immune-based therapeutics. 15 Although MF patients often have a prolonged indolent clinical course of disease that requires localized treatment, there are few effective treatments for the successful management of patients with SS. Because of the lack of success with traditional chemotherapeutic approaches, novel immune-based therapeutics are being developed for use in a multitude of hematologic diseases, including CTCL.…”

Cutaneous T‐cell lymphoma: 2011 update on diagnosis, risk‐stratification, and management

“…Approximately 50% of patients with CTCL, particularly those with advanced stage disease, will ultimately succumb to infectious complications [49][50][51]. Both quantitative and qualitative defects in natural killer (NK) cell [52,53], dendritic cell [54], and T cell-mediated [55][56][57] immunity are observed in CTCL. In addition, CTCL is associated with a significant loss of the T-cell repertoire, analogous to that observed in HIV infection.…”