Method for predicting immune response to neoplastic disease based on mRNA expression profile in neoplastic cells and stimulated leukocytes

Abstract

Tumor necrosis factor (TNF) is capable of inducing apoptosis by interacting with specific TNF receptors on the surface of cancer cells. Because multiple members of TNF ligand and receptor are present within each superfamily, over 300 different ligand-receptor combinations exist. Activated blood leukocytes produce TNF as part of the immune response to cancer, as well as producing chemokines to attract other leukocytes to the site. A method is disclosed of detecting significant induction of a variety of TNF superfamily subtype and chemokine mRNAs in blood leukocytes when whole blood is exposed to heat-aggregated IgG or anti-T cell receptor antibodies as a model of immune system interactions. Substantial individual-to-individual variation is observed in TNF subtypes and chemokines induced. Since peripheral blood leukocytes are the supply of anti-cancer immune cells, the quantitation of ex vivo inducibility of appropriate TNF ligands and chemokines in blood will be useful in individualized cancer immunotherapy. If the tumor mass is small, such as with early invisible metastatic lesions, appropriate TNF assaults may be sufficient to prevent relapse.

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