The inflammatory cytokine network of epithelial cancer: therapeutic implications

A network of inflammatory cytokines and chemokines is found in epithelial cancer. There is evidence that these mediators contribute not only to tumour cell growth and survival, but also to communication between the cancer cells and stromal elements. Tumour cell production of the inflammatory cytokine tumour necrosis factor alpha (TNFalpha) is one critical factor in this autocrine and paracrine network. TNFalpha may also initiate and sustain production of other cytokines and chemokines. Chemokines are key determinants of the leukocyte infiltrate in solid ovarian tumours and influence the extent and phenotype of the infiltrate in ascitic disease. Chemokines may also be involved in tumour cell spread. Thus some of the processes involved in chronic inflammation are also active in human epithelial cancers. Agents that antagonize TNFalpha or chemokines are currently being assessed in preclinical animal cancer models and in phase I clinical trials.