We have studied the effects of anticancer drugs on the immune function of solid tumor patients. Our studies were aimed at determining the relationship between drug effects on patients' suppressor cells and immune function recovery. The results of our studies have demonstrated that """"""""rebound-overshoot immune function recovery"""""""" to greater than pre-treatment levels of function following cytotoxic antineoplastic therapy is due to a selective inhibition of the immunoregulatory cell function of patient monocytes. Those patients who demonstrated """"""""rebound-overshoot"""""""" recovery of immunity did so at a time, following drug therapy, when a previously heightened level of monocyte immunoregulatory cell function was reduced to a normal level. Those patients who, prior to therapy, had normal levels of monocyte immunoregulatory function, were unable to demonstrate """"""""rebound-overshoot"""""""". These results indicate that the functional status of the immunoregulatory cell network, at the time of drug treatment, is a primary determinant of drug action. In the present proposal, we seek to extend these findings. Specifically, we wish to test the following set of hypotheses: 1) That immune function recovery in cancer patients treated with cytotoxic drugs is dependent, in part, on the ability of those drugs to differentially modulate immune cell regulatory and effector function; 2) that such modification would permit a selective enhancement of a range of immune effector functions in the post treatment interval; 3) that patients who demonstrate these effects would also mount objective clinical responses to their tumor while those who do not demonstrate these effects would also not exhibit a comparable clincal tumor response; and 4) that continued administration of cytotoxic chemotherapy would perhaps, in certain patients unfavorably distort the balance between immunoregulatory and effector cell function thereby leading to immune exhaustion and resistence to further antitumor reactivity. We shall do this by evaluating at defined assessment points in disseminated lung cancer and breast cancer patients receiving drug therapy, monocyte associated immunoregulation of lymphocyte and monocyte effector functions. Monocyte immunoregulation studies will focus on the metabolic states of monocytes associated with immune suppression and immune enhancement. Monocyte and lymphocyte effector functions will include assays of mitogen and antigen induced lymphoproliferation, target cell cytotoxicity, and antigen induced leukocyte adherence inhibition. The results of our study will provide information which could be used in the development of therapies seeking to combine cytotoxic drugs with biological response modifiers.
| Braun, D P; Bonomi, P D; Taylor 4th, S G et al. (1987) Modification of the effects of cytotoxic chemotherapy on the immune responses of cancer patients with a nonsteroidal, antiinflammatory drug, piroxicam. A pilot study of the Eastern Cooperative Oncology Group. J Biol Response Mod 6:331-45 |
| Janus, T J; Braun, D P; Harris, J E (1986) Modulation of lymphocyte responsiveness to phytohemagglutinin by micromolecular fibrinogen degradation products. Clin Immunol Immunopathol 41:26-34 |
