Activation of macrophage tumoricidal activity by photodynamic treatment invitro - indirect activation of macrophages by photodynamically killed tumor cells

Macrophages constitute a major part of natural tumor defense by their capac ity to destroy selectively a broad range of tumor types upon specific activ ation. In the last couple of years, these cells have also been implicated a s effector cells in the destruction of tumors by photodynamic therapy. In t he present work, the potential role of macrophage-mediated tumor cytotoxici ty after photodynamic treatment in vitro has been investigated with respect to photodynamic activation of macrophages for tumoricidal effector functio ns. Our data show that photodynamic treatment of highly pure murine bone-ma rrow-derived macrophages with the hematoporphyrin derivative Photosan-3 doe s not result in activation of these cells for cytotoxicity against YAC-1 tu mor cells or secretion of tumor necrosis factor and nitric oxide, irrespect ive of costimulation with interferon-gamma, a potent priming agent for macr ophage antitumoral activity. On the contrary, treatment with higher photose nsitizer doses is found to reduce markedly the viability of the macrophage effector cells. Thus, these results do not lend any support to the hypothes is of direct macrophage activation by photodynamic treatment. However, macr ophages are found to be activated for tumoricidal effector functions indire ctly by photodynamically killed tumor cells, in a way reminiscent of phagoc ytosis-inducing stimuli. It is thus suggested that recognition and phagocyt osis of photodynamically destroyed tumor cells constitutes the major signal for local activation of macrophages in photodynamically treated tumor tiss ues, which may be crucial for final, specific eradication by the immune sys tem of tumor cells surviving photodynamic treatment. (C) 1999 Elsevier Scie nce S.A. All rights reserved.