The effects of chemotherapeutics on cellular metabolism and consequent immune recognition

Abstract

Awidely held view is that oncolytic agents induce death of tumor cells directly. In this report we review and discuss the apoptosis-inducing effects of chemotherapeutics, the effects of chemotherapeutics on metabolic function, and the consequent effects of metabolic function on immune recognition. Finally, we propose that effective chemotherapeutic and/or apoptosis-inducing agents, at concentrations that can be achieved physiologically, do not kill tumor cells directly. Rather, we suggest that effective oncolytic agents sensitize immunologically altered tumor cells to immune recognition and immune-directed cell death.

Figure 1

Distribution and Level of Fas in L1210/0 and L1210/DDP Cells. Expression of cell-surface Fas, leftmost panels, and intracellular Fas, right most panels in L1210/0, upper two panels, and L1210/DDP cells, lower two panels. The levels of cell surface Fas (dark lines) were determined using fluorochrome conjugated anti-Fas antibodies (Pharmingen Inc.) and flow cytometry. The levels of intracellular Fas were determined subsequent to cellular permeabilization and fixation. The Fas levels are measured relative to staining for fluorochrome-conjugated isotype control (grey lines).

Figure 2

Adriamycin Induced Increase in B7.2 Expression. Expression of the cell-surface co-stimulatory molecule B7.2 as a function of treatment with adriamycin. The level of cell-surface B7.2 was determined using fluorochrome conjugated anti-B7.2 antibodies and flow cytometry. The B7.2 levels are measured relative to staining for fluorochrome-conjugated isotype control.