Leukocyte activation in advanced cancer as an explanation for absent leukocyte adherence inhibition to cancer extracts and chemoattractant

Abstract

Tube leukocyte adherence inhibition (LAI) measures human immunity by antigen-binding leukocytes releasing chemoattractant-like mediators that are the ultimate inhibitors of adherence by bystander leukocytes. We determined whether the absent LAI responses to cancer extracts for patients with large body burdens of bladder cancer was related to a defect in antigen binding or chemoattractant responsiveness. Leukocytes from patients with small body burdens of bladder cancer gave positive LAI responses of a similar extent to either bladder cancer extracts or chemoattractant [ n-formyl- l-methionylleucylphenylalanine (FMLP)]. Of the adherent leukocytes, about 20–30% became non-adherent with a positive LAI response: monocytes, neutrophils and lymphocytes responded. In the control tubes, leukocytes from patients with large body burdens of bladder cancer were more non-adherent and about 15% less adherent than leukocytes from controls or patient with early cancer. They showed no further decrease in adherence, or conversely increase in non-adherence, with either extracts of bladder cancer or FMLP. The leukocytes also failed to transduce transmembrane signals to the same stimuli. The defect was reversible since PGE 2 restored the adherence of leukocytes to normal, and subsequently they exhibited membrane potential changes and about 34% non-adherence to either bladder cancer extracts or FMLP. From these results we conclude that chemoattractant LAI-responsive leukocytes from patients with large body burdens of bladder tumor are activated in vivo, probably by mediators from inflammatory cells.