The prognostic value and function of CD103+ tumor infiltrating lymphocytes

Terwindt, A. (Anouk) (2016) The prognostic value and function of CD103+ tumor infiltrating lymphocytes. thesis, Medicine.

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Abstract

Background: The presence of tumor infiltrating lymphocytes (TILs) is associated with better prognosis in high grade ovarian carcinoma (HGSC), mostly due to epithelial CD8+ cells and CD103+ cells. As the influence of the stromal CD8 remains unclear, we aim to define the prognostic value of these cells and compare the prognostic value of CD103 to CD8 in the epithelium, stroma and total. Furthermore, we aim to further research the function of CD103+ cells, as it remains unclear. Besides, we researched the possible therapeutic value of CD103+ cells by studying the potential for Adoptive Cell Transfer (ACT). Methods: Prognostic value of CD8 and CD103 was assessed by scoring of tissue microarrays (TMA) and correlation of the scores with survival. The functional side of CD103+ was studied by co-culturing peripheral blood mononuclear cells (PBMC) with HGSC cell lines or TGF-β. The cells were stained and assessed by flowcytometry. Furthermore, tumor infiltrating lymphocytes were extracted from tumors obtained at surgery, cultured ex vivo and assessed by flowcytometry for expansion and T-cell markers. Results: No correlation was found between survival and stromal CD8, epithelial CD8 and total CD8. CD103+ score was significantly correlated with disease-specific survival. CD103+ integrin was up regulated on PBMCs in the functional experiments. CD103+ cells had an active phenotype and were capable of robust cytokine production, making them interesting for ACT. TILs from digest-culture had an active phenotype, however, lacked proliferation. Conclusions: CD103 is preferable as a prognostic marker over epithelial CD8The CD103+ subset has an active phenotype and is capable of robust cytokine production both in the functional experiments and the TIL cultures. However, more research must be done before CD103+ cells can be used for cell transfer, as they did not proliferate in culture.

Item Type:	Thesis (Thesis)
Supervisor name:	Faculty supervisor: and Nijman, Professor dr. H.W. and Second supervisor: and Bruyn, Dr. M. de and Department of Gynecological Oncology, UMCG
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 10:45
Last Modified:	25 Jun 2020 10:45
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/643

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