Expression of the leukocyte chemoattractant chemerin in human prostate tumors.
81 Background: The infiltration of immune cells into the tumor microenvironment can regulate growth and survival of neoplastic cells. Several studies have shown a correlation between increases in the number of effector immune cells present in a tumor and clinical outcomes in many human tumors, including prostate. The field of prostate cancer immunotherapy continues to grow, with sipuleucel-T already approved and a recombinant vaccinia-PSA (Prostvac) currently in a Phase III clinical trial. Recent studies have shown immune cell infiltration into prostate tumors after systemic administration of sipuleucel-T, suggesting infiltration of these cells may be a key step in the mechanism of action. Methods: Here, in a survey of public whole genome expression datasets we found that the gene for chemerin (RARRES2), a widely expressed endogenous chemoattractant protein for immune cells, is downregulated in prostate cancer. In mouse models, we have previously shown that forced re-expression of chemerin at sites of tumor results in an increase in immune cell infiltration (e.g. NK and T cells), as well as significantly reduced tumor growth (Pachynski JEM 2012). Results: In addition to this published analysis, using RT-qPCR we have gone on to confirm that human prostate tumors have significantly less chemerin (RARRES2) compared to normal prostate tissue. Preliminary immunohistochemistry results in human tumors using an anti-human chemerin antibody, are consistent with our qPCR results, suggesting human prostate tumors downregulate chemerin during their malignant transformation. Conclusions: We have shown, for the first time, that human prostate tumors downregulate chemerin compared to normal prostate tissue. We hypothesize that this is one mechanism of “immune escape.” Therapeutic forced re-expression of chemerin in human tumors may restore anti-tumor immunity within the tumor microenvironment resulting in slowed growth and regression of established tumors. Additionally, chemerin’s ability to recruit NK and T cells into the tumor microenvironment may make it an ideal therapy to combine with other treatments aimed at boosting the immune response, such as sipuleucel-T or checkpoint inhibition (e.g. anti-CTLA4, anti-PD1/PDL1).