The present invention pertains to novel modulators of tumor resistance against T-cell mediated cytotoxic immune responses. The invention provides antagonists of tumor immune escape mechanisms and methods and other aspects related thereto, and therefore provides novel approaches for treating or aiding a treatment of various cancerous diseases and/or the diagnosis thereof. The invention specifically discloses C-C chemokine receptor type 9 (CCR9) as a checkpoint molecule in tumor resistance against cytotoxic T-cells. Provided is the inhibition of CCR9 expression, CCR9 signalling and/or CCR9-T-Cell interaction and inhibitors or antagonists thereof. In particular aspects, the invention provides combination therapeutics and/or therapies involving such inhibitors or antagonists. The invention furthermore provides screening methods for novel cancer therapeutics modulating CCR9 action, diagnostic approaches to detect cancer resistance to cytotoxic T-cells as well as pharmaceutical compositions and diagnostic kits for performing, for use with or related to these methods.
