Rachel Evans

King's College London | KCL · Division of Cancer Studies

Over the past decade, immunotherapy delivered novel treatments for many cancer types. However, lung cancer still leads cancer mortality, and non-small-cell lung carcinoma patients with mutant EGFR cannot benefit from checkpoint inhibitors due to toxicity, relying only on palliative chemotherapy and the third-generation tyrosine kinase inhibitor (TK...

In vivo delivery of small molecule therapeutics to cancer cells, assessment of the selectivity of administration, and measuring the efficacity of the drug in question at the molecule level, are important ongoing challenges in developing new classes of cancer chemotherapeutics. One approach that has the potential to provide targeted delivery, tracki...

Lymphatic vasculature is crucial for metastasis in triple-negative breast cancer (TNBC); however, cellular and molecular drivers controlling lymphovascular metastasis are poorly understood. We define a macrophage-dependent signaling cascade that facilitates metastasis through lymphovascular remodeling. TNBC cells instigate mRNA changes in macrophag...

Despite decades of research in the epidermal growth factor receptor (EGFR) signalling field, and many targeted anti-cancer drugs that have been tested clinically, the success rate for these agents in the clinic is low, particularly in terms of the improvement of overall survival. Intratumoral heterogeneity is proposed as a major mechanism underlyin...

Cancer cells tend to metastasize first to tumor-draining lymph nodes (LN), but the mechanisms mediating cancer cell invasion into the lymphatic vasculature remain little understood. Here we show that in the human breast tumor microenvironment (TME) the presence of increased numbers of RORγt+ group 3 innate lymphoid cells (ILC3) correlates with an i...

Angiogenesis is essential for tissue development, wound healing and tissue perfusion, with its dysregulation linked to tumorigenesis, rheumatoid arthritis and heart disease. Here we show that pro-angiogenic stimuli couple to NADPH oxidase-dependent generation of oxidants that catalyse an activating intermolecular-disulphide between regulatory-RIα s...

Within breast cancers, trans-endothelial migration of tumour cells through lymphatic vessels is the first step to tumour dissemination and lympho-vascular invasion has been shown to stratify breast cancer phenotypes into distinct prognostic groups. The exact molecular mechanisms mediating tumor cell entry and persistence within the lymphatic system...

+hi CD23 hi CD24 hi ) similar to that described for regulatory B cells (Bregs). The increase in this B cell subset was mirrored by an increase in CD4 + Tregs. The growth of new lymphatic vasculature was observed in 4T1.2 tumours in vivo at multiple time-points through use of the mammary imaging window. In 4T1.2 tumour bearing mice we observed new l...

T lymphocytes have an essential role in adaptive immunity and rely on the activation of integrin lymphocyte function-associated antigen-1 (LFA-1) to mediate cell arrest and migration. In cancer, malignant cells modify the immune microenvironment to block effective host antitumor responses. We show for the first time that CD4 and CD8 T cells from pa...

Natural killer (NK) cells kill tumor cells and virally infected cells, and an effective NK cell response requires processes, such as motility, recognition, and directional secretion, that rely on cytoskeletal rearrangement. The Rho guanosine triphosphatase (GTPase) Cdc42 coordinates cytoskeletal reorganization downstream of many receptors. The Rho-...

The integrin lymphocyte function-associated antigen 1 (LFA-1) controls many functions of T lymphocytes and is particularly essential during lymphocyte migration from blood into tissues. LFA-1 is considered to initiate "outside-in" signaling when bound to ligand intercellular adhesion molecule 1 (ICAM-1), but little is known about the proteins invol...

914 T lymphocytes have an essential role in adaptive immunity and rely on tightly regulated signaling through integrin lymphocyte function-associated antigen (LFA)-1 to migrate into lymph nodes and interact with antigen-presenting cells. Malignant cells modify their immune microenvironment to prevent effective host anti-tumor responses, promote tum...

Integrins are the major adhesion receptors of leukocytes and platelets. Beta1 and beta2 integrin function on leukocytes is crucial for a successful immune response and the platelet integrin alpha(IIb)beta3 initiates the process of blood clotting through binding fibrinogen. Integrins on circulating cells bind poorly to their ligands but become activ...

A successful immune response depends on the capacity of immune cells to travel from one location in the body to another--these cells are rapid migrators, travelling at speeds of microm/minute. Their ability to penetrate into tissues and to make contacts with other cells depends chiefly on the beta2 integrin known as LFA-1. For this reason, we descr...

Ovarian cancer is the fourth most common cancer in women in the Western world. In a pilot scale study, we highlight changes in the total serum glycome of patients with advanced ovarian cancer that might shed insight into disease pathogenesis. These changes include increases in levels of core fucosylated, agalactosyl biantennary glycans (FA2) and si...