Use this URL to cite or link to this record in EThOS:
Title: Immune reactions in lymph nodes and ovarian cancer
Author: Johnson, Sarah Christina
ISNI:       0000 0005 0287 2010
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2019
Availability of Full Text:
Access from EThOS:
Access from Institution:
During adaptive immune response, the lymph node (LN) volume may increase, but the impact on T cell (TC) trafficking and interaction are unknown. Lymphangiogenic LNs are associated with poor prognosis in cancer patients, in addition to presenting with impaired anti-tumour immune responses. Lymphatic vessels (LVs) can respond to lymph-born signalling molecules and secrete agents that can impact the response at the LN. Two studies were conducted to gain insight into immune response changes; first, in the LN due to LN swelling and second, in LVs of ovarian cancer patients. The first study involved using an agent-based model to describe the TCs response to antigen presenting dendritic cells in the LN paracortex while modulating the paracortex swelling behaviour. The expression of TC receptor Sphingosine-1- phosphate-1 receptor (S1P1r) was also modulated and the effector TC response analysed under different swelling conditions. This showed that paracortical swelling can aid TC activation but can inhibit effector CD8+ TCs production if the swelling occurs too early in the proliferative response. S1P1r- mediated retention of newly differentiated effector TCs increased the effector TC response. The second study investigated LV changes from ovarian cancer patients using immunohistochemistry to quantify LV inflammatory status, identify cancer-cell infiltration and analyse changes in miRNA expression. Patient relapse was associated with high LV inflammation away from the tumour site. In addition, several miRNA groups, including the let-7 family, may present as prognostic and therapeutic targets.
Supervisor: Moore, James Sponsor: National Institutes of Health
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral