HUMAN TUMOR-CELLS, MODIFIED BY A NOVEL PRESSURE CROSSLINKING METHODOLOGY, PROMOTE AUTOLOGOUS LYMPHOCYTE-PROLIFERATION AND MODULATE CYTOKINESECRETION/

Hydrostatic pressure (P) combined with membrane protein crosslinking ( CL) by adenosine dialdehyde (AdA) can render tumor cells immunogenic. We have recently shown that PCL treatment of murine tumor cells augmen ted the presentation of MHC-restricted tumor-associated antigens and e nhanced cell-mediated immunity. In cancer patients inoculated with aut ologous PCL-modified tumor cells, a significant delayed-type hypersens itivity response was elicited. Since the balance between cell-mediated immunity and humoral immunity is reciprocally controlled by immunoreg ulatory cytokines, we have examined the proliferative response and cyt okine secretion pattern in cultures of human peripheral blood mononucl ear cells (PBMC) stimulated by autologous PCL-modified and unmodified tumor cells. These tumor cells were obtained from freshly resected tum or tissue of 16 patients with colon (8), lung (4) and renal (4) carcin omas. The results demonstrated that PCL-modified tumor cells promoted an increase in PBMC proliferation in 5 out of 8 (63%), 1 out of 4 (25% ) and 4 out of 4 (100%) colon, lung and renal cell carcinomas. Fourtee n of the above cultures were also analyzed for the secretion of interl eukin-10 and interferon-gamma. Overall, a substantial decrease in IL-1 0 secretion was detected in 9 out of 14 (64%) cultures while a recipro cal increase in interferon-gamma secretion was noted in 8 out of 14 (5 7%) cultures. Our results confirmed that PCL-modified human tumor cell s of different etiologies can modulate the pattern of cytokines releas ed from stimulated autologous lymphocytes. Such a procedure could prov e valuable in the production of autologous tumor vaccines.