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Freier, Christoph (2016): Role of regulatory T cells and associated chemokines in human gynecological tumors. Dissertation, LMU München: Medizinische Fakultät



Purpose: To assess the clinical significance of different Treg attracting chemokine intratumoral expressions in breast and ovarian cancer patients with available long-term follow-up (15 years). We investigated the prespecified hypothesis that the expression of Treg specific chemokines in cancer tissue predicts the OS. Patients and Methods: We screened all so far known chemokines of the CC-family for their capacity to selectively attract Treg in vitro. Three chemokines (CCL1, CCL22, and CCL27) with selective action on Treg migration were stained using extensively characterized antibodieAntibodys. The numbers of positive cells in tissue microarray cores from ovarian cancer and invasive breast cancer were computer-aided determined. Results: Within all analyzed chemokines, only CCL1, CCL22 and CCL27 selectively attracted Treg in vitro. All three chemokines were strongly expressed in most ovarian and breast cancer tissues. Moreover, there was a significant relationship between Treg infiltration in tumors and CCL1- and CCL27-expressing cell total numbers, whereas no association was seen for CCL22. High numbers of CCL1- or CCL27-positive cells identified patients with shorter OS. Conclusion: Our findings indicate that quantification of intratumoral Treg attracting chemokines in ovarian and breast cancer is valuable for assessing disease prognosis. Unlike conventional clinicopathologic factors, high expression of certain chemokines can identify patients at risk of death over 15 years. CCL1 and CCL27 represent novel markers for identifying effect of immune response and tumor escape as well as patients who may benefit from immunotherapy. Such chemokines may gain to be considered together and could represent important therapeutic targets.