P40: Does IL8 (CXCL8) have a role in thymoma progression and as a marker for relapse?

Abstract: Thymomas are rare tumours of thymic epithelium for which surgical resection is the definitive treatment. The thymus is the organ in which T cells mature. During development in the thymus, T cells acquire their unique T cell receptor (TCR) through somatic recombination. Mature naive T cells that exit the thymus harbour small circles of DNA that are by-products of somatic recombination known as TCR excision circles (TRECs). Although stable, TRECs are not replicative and hence are a marker of recent thymic emigrants (RTEs). We have recently shown that thymocytes and subsequently RTEs, unlike more mature peripheral blood T cells, produce the cytokine interleukin 8 (IL8/CXCL8). This ability appears to be lost with repeated stimulation and expansion. Therefore, T cell production of IL8, like TREC levels, is a marker of RTEs and thymic activity. Our recent data proposes two questions in relation to this tumour type: (I) Could IL8 together with TREC levels act as a biomarker for tumour recurrence? (II) Does IL8 have a role as a growth factor for thymoma? After resection, macroscopic recurrence is usually detected in patients by active surveillance with serial axial imaging. There is some data in the literature to suggest that TREC levels are higher in patients with recurrence compared to those without. This raises the possibility of using RTEs to aid in surveillance and guide the judicious use of imaging. Our initial data suggests that even after R0 margins, both TRECs and IL8 producing T cells can be detected in the periphery, albeit at very low levels. However, we hypothesize that intra-patient monitoring of TREC levels and IL8 producing T cells may still be useful as a biomarker for recurrence. Moreover, the fact that IL-8 is associated with tumour maintenance through its functions in angiogenesis; cancer cell growth and survival; and modification of immune responses, indicates that this may be an important growth factor in thymoma. We hope to address this using resected material in comparison with normal thymuses.

Keywords: Biomarker; T cell receptor excision circle (TREC); recent thymic emigrant (RTE); interleukin 8 (IL8)