Cytotoxicity in vitro of blood lymphocytes from bladder cancer patients and controls to allogeneic or autologous tumor cells derived from established cell lines or short‐term cultures

Abstract

Blood lymphocytes from small groups of patients with transitional-cell carcinoma of the urinary bladder (TCC), clinical controls (CC) or healthy donors (HD) were tested for cytotoxicity in vitro by a 51Cr-release assay. The target cells were either from TCC or control tissue (long-term cultures) or were from short-term TCC cultures, kept in vitro for 10-20 transfer generations. When tested with allogeneic target cells from long-term cultures, TCC patients' lymphocytes tended to be more cytotoxic to TCC targets than to control targets. For the control lymphocytes this was not seen. A large proportion but not all of the cytotoxicity to these target cells was due to immunoglobulin-dependent cellular reactions, probably mediated by natural and disease-related antibodies of the lymphocyte donors, since it was significantly inhibited by Fab-fragments of rabbit antibodies to human immunoglobulin. Moreover, it was, to a large extent, mediated by lymphocytes with Fc-receptors for IgG. For seven of the TCC target cell cultures (two long-term and five short-term) autologous lymphocytes were also available for testing. While two patients were non-reactive to their own tumor cells, five reacted strongly in the autologous combinations. These autologous reactions were immunoglobulin-independent and were mediated by Fc-receptor-negative effector cells. In some instances, autologous cytotoxicity was accompanied by similar reactions to some of the allogeneic TCC targets but not to the allogeneic non-TCC control targets. On the basis of available information on HLA antigens in this material, the pattern of cross-reactions suggests that the cytotoxicity encountered in the autologous and in some of the allogeneic TCC-combinations may be the expression of antibody-independnet but specific CTL-mediated reactions, regulated by HLA. However, at the present stage of the investigation, other mechanisms must also be considered since the target cells from short-term TCC cultures were sometimes lysed by control lymphocytes in immunoglobulin-independent reactions. Whatever the explanation, the results show that the cytotoxicity observed in the in vitro systems is usually the net result of several different types of reaction. Which effector cell types and which mechanism of recognition will predominate in a given lymphocyte/target cell combination is greatly influenced by the nature and origin of the target cells used.

Spontaneous cell-mediated cytotoxicity in patients with transitional cell carcinoma of the urinary bladder

“…It seems therefore that the effector cell types and mechanism of target recognition may vary with the nature of the target cells. Our results demonstrating the killing of K-562 and T leukemic cells (Peer) by T lymphocytes from TCC patients may add to the evidence previously brought forward [34] that the cytotoxicity observed in the in vitro systems is usually a result of several different types of reactions.…”

“…The latter may reflect reactions against one or more tumor-associated antigens, and do not correlate with reactions against allogeneic bladder tumor lines [33]. However, other mechanisms have also been considered [34]. It seems therefore that the effector cell types and mechanism of target recognition may vary with the nature of the target cells.…”

Lymphocyte‐mediated lysis of tumor cells in vitro (ADCC), induced by serum antibodies from patients with urinary bladder carcinoma or from controls

“…As reported elsewhere, a different antibody-independent type of cytotoxicity, exhibited by Fc-receptor-negative effector cells, is seen in autologous lymphocyte/tumor cell combinations. This was also predominating when bladder tumor cells derived from short-term cultures were used as target cells (Troye et al, 1980b). Nevertheless, the concept that lymphocyte cytotoxicity may frequently be the expression of an antibody-mediated cellular cytotoxicity (ADCC) induced by the donor's own antibodies, is also supported by findings recently reported by others (Akira and Takasugi, 1977;Koide and Takasugi, 1977;Koide et al, 1978).…”

Humoral and cellular immune reactions against tumor cells in patients with urinary bladder carcinoma

“…The tumor-related cytotoxicity is most pronounced for groups of patients with moderate tumor burden [18,19,31] or low tumor invasiveness [37, 38; for further references and discussion see 35]. These findings by no means exclude the existence in TCC of a non-immunoglobulin-dependent lymphocyte-mediated cytotoxicity, particularly in autologous lymphocyte/target cell combinations [32,40,42]. Depending on the assay conditions, this appeared to be true for both allogeneic and autologous lymphocyte/target cell combinations [39].…”