Natural killer cell‐mediated lysis of freshly isolated human tumor cells

Abstract

Studies on interactions between natural killer (NK) cells and freshly isolated human tumor cells are still relatively scarce. With respect to the understanding of NK cell interactions with human tumors in vivo, and attempts to better predict the outcome of NK cell-mediated adoptive immunotherapy, such studies merit further attention. They may provide information that is not readily evident through studies of human tumor cell lines established through long-term culturing in vitro. The latter undergo several changes and adaptations to their environment, many of which may affect interactions with NK cells. Studies of NK cell interactions with freshly explanted human tumors, however, are cumbersome for several reasons including; often poor accessibility of human tumor material per se, difficulties in sample processing and contamination of tumors with nontumor cells, spontaneous apoptosis of tumor cells, as well as methodological challenges in assessing tumor cell lysis following interactions with NK cells. Here, we review the current knowledge on NK cell interaction with freshly isolated human tumors.

Reduced DNAM-1 expression on bone marrow NK cells associated with impaired killing of CD34+ blasts in myelodysplastic syndrome

“…41,42 NK-cell recognition of myeloma seems to depend primarily on DNAM-1, whereas recognition of AML primarily relies on NKG2D. 21 Similarly, a role for NKG2D has been suggested in NK cellmediated killing of the MDS clone. 25,43 However, those experiments were based on one MDS cell line (MDS1) and not on primary blasts.…”

“…In contrast, by studying the recognition of freshly isolated blasts, we show a dominant role for DNAM-1 in the recognition of MDS. Given the crucial role for DNAM-1 and NKG2D in the recognition of several human tumors 21 and in immune surveillance against tumors in mice, 19,20 it is tempting to speculate that reduced expression of these receptors may have consequences in the disease progression and in the malignant transformation of MDS to AML. …”

“…18 Recent studies, based on mouse models, have shown a crucial role for DNAM-1 and NKG2D in immune surveillance of neoplastic cells. 19,20 Although there is no direct evidence for the role of DNAM-1 and NKG2D in tumor immune surveillance in humans, data clearly indicate that these receptors are important for the recognition of a broad variety of human tumors (reviewed in Carlsten et al 21 ). In addition, reduced surface expression of DNAM-1 and NKG2D has recently been observed and associated with impaired NK-cell cytotoxicity in patients with advanced cancer.…”

Primary Human Tumor Cells Expressing CD155 Impair Tumor Targeting by Down-Regulating DNAM-1 on NK Cells

“…These studies provide the first direct evidence for a central role for DNAM-1 in tumor immune surveillance. DNAM-1 is important for NK cell-mediated recognition of several human tumors, including neuroblastoma, myeloma, and Ewing sarcoma (16,17,29,35). We have previously shown that the DNAM-1/CD155 interaction is crucial for the recognition of freshly isolated ovarian carcinoma by allogeneic NK cells (15).…”

The immunomodulating roles of glycoproteins in epithelial ovarian cancer

“…From the perspective of ovarian cancer, the NKG2D and DNAM-1 receptor systems are of importance because ovarian tumors express ligands for these two receptors (23,(71)(72)(73)(74)(75). It has been proposed that naïve or activated autologous NK cells can mediate cytolysis of ovarian tumors because of the expression of NKG2D and DNAM-1 ligands by ovarian tumors (76). However, it should be noted that the killing of ovarian tumor cells by NK cells is significantly lower than the killing observed with NK cell susceptible targets ( Figure 3).…”