The role of chemokines in lymphocyte infiltration in ovarian cancer: from MRNA microarray to tissue microarray

Introduction: High numbers of CD8+ cytotoxic T lymphocytes (CTL) are associated with a survival advantage in ovarian cancer. Chemokines may play a role in T lymphocyte recruitment to the tumor, but they are also linked to metastasis and angiogenesis. Aim: To determine to what extent chemokines are involved in lymphocyte infiltration of ovarian cancer. Methods: We used microarray technology to rank chemokines based on their differential expression levels between tumors with many and few tumor infiltrating CTL. Next, we further investigated these results using immunohistochemistry and cytokine bead arrays. Results: Six chemokines and chemokine receptors were differentially expressed between 24 CTL high and 35 CTL low tumors. Based on these data and previous literature, we selected CXCL9, CXCL10, CXCL6 and CXCR6 for further validation. Stainings for these chemokines were performed on 254 tumor samples using tissue microarrays. There were no associations between chemokine (receptor) staining intensity and CTL infiltration. However, for CXCL10, high expression was associated with high stage, serous tumors, and >2 cm residual tumor after surgery. In univariate survival analysis, CXCL10 was associated with a worse prognosis. Next, we analyzed soluble CXCL10 at the serum level. For 98 patients, both tissue and serum were available. There were no associations between CXCL10 staining and serum concentrations. However, we found a positive correlation between CXCL10 in serum and CTL infiltration in the tumor. Conclusion: After validation of microarray results, we found a very limited role for chemokines in lymphocyte migration. However, CXCL10 is implicated in more aggressive tumor behavior