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Browsing by Subject "RCC"

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  • Immunophenotyping and expanding tumor infiltrating lymphocytes in renal cell carcinoma 
    Uski, Ilona (2021)
    Tumors contain variable number of different immune cells that infiltrate the tumor microenvironment, such as tumor infiltrating lymphocytes (TILs). More research is needed to understand the functional and clinical importance of various TIL subgroups in cancer. Understanding the differences between individual cancer patients will help development of new treatment methods and discovering why only some patients respond to immunological treatments. Renal cell carcinoma (RCC) is the most common kidney cancer type with good overall survival prognosis when the tumor is surgically removed before it has metastasized. However, the prognosis of RCC is significantly decreased when the cancer has spread. The aim of this master’s thesis project was to characterize the tumor infiltrating lymphocyte populations in patient derived RCC samples. Characterization was done with flow cytometry and a custom antibody panel designed to detect various lymphocyte subpopulations. We also wanted to further study the TILs by expanding the lymphocytes from the tumor samples and test their function in an impendence-based assay against matched autologous tumor cells. Based on the flow cytometry results, the different RCC subtypes in the cohort showed some variation in TILs. Still, more research is needed to investigate these differences. We were able to culture the TILs from the RCC tumor samples, and most of them were CD4+ T cells expressing memory markers CD45RO and CCR7. Some expanded TILs expressed markers related to T cell activity and terminal differentiation. In conclusion, this thesis provided material and insights for future RCC TIL experiments as well as considerations for optimization needed in further studies.
  • Tumörorganoider från patienter som testplattform för onkolytisk virusterapi 
    Feodoroff, Michaela (2020)
    Within the field of cancer immunotherapy, immune checkpoint inhibitors have been a revolution since they provoke re-activation of T-cell immune responses towards cancer. Despite their success, they only work in 13% of the patients because of a poorly immunogenic tumor, mostly due to weak T-cell infiltration. Oncolytic viruses have shown the ability to work in synergy with checkpoint inhibitors because of their tumour-specific tropism, innate immunogenicity and ability to secrete immunostimulatory agents into the tumor microenvironment. Regardless of the great potential, we lack suitable pre-clinical models to test this effect. In this study we developed renal cell carcinoma-derived organoids as in vitro platforms due to their high pre-clinical predictability compared to that of murine and in vitro 2-dimensional cell culture models. To test the ability of oncolytic viruses to stimulate the immune system, we generated three cytokine-expressing (CXCL9, CXCL10 and IL-15) oncolytic adenoviruses using a novel cloning method that we developed. We have shown that these viruses successfully produce high amount of the cytokine and attract peripheral blood mononuclear cells freshly isolated from Buffy coats. Genetically modified oncolytic adenoviruses were also shown to infect and kill human renal cell carcinoma organoids. Together, our results demonstrate the potential of organoids as test platforms for oncolytic virus -based therapy and the importance of adequate cytokine expression in T-cell recruitment. The tumor organoid platform we developed will be useful for advancing patient-specific treatment strategies and serve as a base for innovative immunotherapy models.

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