Several chemokines and cytokines are implicated in CRC immune response. One of the under examined features of CRC is the regulation of anti-tumor immunity by atypical chemokine receptor 4 (ACKR4) expression. This receptor, is involved in the internalization and degradation of multiple chemokines, such as chemokine (C-C motif) ligand 19 (CCL19) and CCL21, thereby modulating the CC-chemokine receptor 7 (CCR7)/CCL19/CCL21 chemotaxis and its downstream immune responses. We are testing the hypothesize that ACKR4 positively affects immune regulation in CRC and confers antitumor immunity by modulating CCR7/CCL19/CCL21 chemotaxis. The results from this pilot study will establish the clinical significance of ACKR4 expression levels to immune response in colorectal cancer. As an outcome, it will fundamentally advance our knowledge of how anti-tumor immunity was generated and regulated in CRC, and provide novel targets for CRC immunotherapies.
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