Surgery (Austin & Northern Health) - Theses

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Subject: prostate cancer × Author: Rajarubendra, Nieroshan ×

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    Profiling tumour infiltrating lymphocytes in prostate cancer
    Rajarubendra, Nieroshan ( 2013)
    The purpose of this study was to understand the T cell processes that take place in prostate pathology. The subset of T cells and their functional and activational status was determined using flow cytometry and immunohistochemistry. Furthermore the use of androgen deprivation therapy (ADT) on the impact on T cells was also determined. The three main conditions of prostate pathology investigated were benign prostatic hyperplasia (BPH), chronic abacterial prostatitis (CAP) and prostate cancer (PCa). Patients with BPH were used as the control group. The results in CAP showed a trend of an active immune process, where there was an influx of CD4+ T lymphocytes cells (9.45%, p 0.1407) in prostate tissue and a reduction in T regulatory (Treg) cells (2.32%, p 0.0675) in the tissue and the blood (3.13%, p 0.0042). In PCa tissue there was an influx of both CD4+ T lymphocytes (9.63%, p 0.0296) and CD8+ lymphocytes (12.81%, p 0.0063). Correspondingly a trend was seen with an increase in Treg cells in prostate tissue (2.12%, p 0.2480). This resulted in the ratios between CD4:CD8, CD4:Treg and CD8:Treg in PCa to be similar to BPH indicating a net homeostasis in immune action. The use of Treg cells as a prognostic indicator was compared to current pathological markers, where a higher number of Treg cells was seen in patients with extraprostatic spread (3.52%, p 0.0371), seminal vesicle extension (10.74%, p 0.0249), PSA relapse (4.39%, p 0.0162) and higher Gleason score (3.89%, p 0.0376). Despite showing a homeostatic picture in PCa, the functional status of CD8+ T lymphocytes was assessed. There were lower proportions of naïve T cells (9.86%, p 0.0068) and central memory T cells (8.60%, p 0.0258) in PCa tissue. While there was an increase in terminal effector T cells (12.06%, p 0.0019) and effector memory T cells (8.63%, p 0.0253). This implied that the tumour cells had been recognized and a shift in the dynamics towards a local cytotoxic environment. These cytotoxic T lymphocytes were activated as demonstrated by increased expression of CD69 (13.35%, p 0.0083). Despite showing activation, the effectiveness of these cells in the implementation of an anti-tumour response was assessed by evaluating the distribution of cytokines IFNγ, TGFβ and IL-10. However no clear pattern was seen, but it will require further investigation with a larger sample population. The use of ADT has been shown to reverse thymic involution and restore peripheral T cell population. However from this study there was no difference seen in the subset numbers, functional and activational status of T lymphocytes. From this study, the profile of prostatic pathology is better understood. The T cell profile especially in the in the local tumour environment of PCa shows a dynamic process between cytotoxic and immunosuppressive cells. This will allow for the development of further studies to understand the immune interaction with PCa.