High-dimensional (HD) photonic quantum information (QI) promises considerable advantages compared to the two-dimensional qubit paradigm, from increased quantum communi¬cation rates to increased robustness for entanglement distribution. This project aims to unlock the potential of HD QI by encoding information in the spectral-temporal (ST) degrees of freedom of light. We will develop matched experimental tools and theoretical archi¬tectures for manipulating and characterizing such states, and we will demonstrate their use in applications. Every light beam has a large capacity for information coding in its ST degrees of freedom, which, through broadband optical fiber communications, underpins the massive capacity of the internet. Quantum light beams inherit this capacity, which has been as-of-yet underexplored and underutilized. ST control of quantum states of light enables multiplexing of QI in a single spatial mode, ideally suited for guided-wave communications and integrated devices. QI encoding in HD states, going well beyond two-dimensional encoding, has been recognized as a promising way towards enhanced QI processing, communication, and sensing. Even with an increasing number of theoretical proposals, there are, however, few experimental demonstrations of this capability. What is needed is a unified theoretical approach to HD quantum states that is relevant to real experimental devices, accounting for real-world imperfections in order to unlock the full potential of ST-encoded HD QI processing. This project will deliver such a joint effort to bridge this gap. We will carry out connected theoretical and experimental research to achieve secure communication in bipartite and multipartite scenarios, enhance the performance of quantum networks, and develop efficient methods for dimension witnesses, entanglement certification, estimation of properties of quantum states and channels, and quantum metrology. Moreover, we will introduce and develop the new concept of HD quantum temporal imaging. Experimental implementation will be based on novel HD encodings in time and frequency based on ultrafast quantum optical approaches in nonlinear waveguide and electro-optic devices. Encodings using broadband field-orthogonal overlapping pulse modes as well as distinct, non-overlapping time and frequency bins will be explored and brought together to form an effective hybrid-encoded network. Key to experimentally accessing the HD potential of the ST encoding will be the noiseless manipulation of time scales using the concepts of quantum temporal imaging. Combined experimental and theoretical efforts will yield a unified platform for HD, integrated optical QI processing, communication, and sensing. Our project has direct relevance to three Target Outcomes addressed in the QuantERA call, namely, quantum communications (QC), quantum information sciences (QIS), and quantum metrology, sensing and imaging (QMSI). For QC target outcome, we are aiming to develop new communication protocols based on high-dimensional encodings of pulse modes and time-frequency bins with functionality enhanced by quantum effects. We shall also investigate quantum networks in higher dimension. With respect to QIS target outcome, we shall investigate several concepts in quantum information for higher-dimensional quantum systems, ranging from entanglement detection and Bell-inequality violation to efficient estimation of quantum states and properties of quantum channels. Regarding the QMSI target outcome, we intend to develop a new kind of quantum imaging – quantum temporal imaging – directly inspired by its spatial counterpart. We shall also develop the detection schemes that are optimised with respect to various components of the QC network.

Glioblastoma Multiforme(GBM) is a highly malignant brain tumour with many patients surviving less that a year. Even with maximum surgery, chemotherapy and radiotherapy less than half of patients will survive 2 years and only 6% will be alive at 5 years. Therefore there is an urgent need for new treatments. Boosting the immune system's natural ability to fight cancer using dendritic cells has shown promise in some patients. Dendritic cells (DC) are particular white cells which mobilise other immune cells (killer T-cells) to recognise and kill cancer cells. DC can be made in a laboratory using a patient's own white cells (monocyte derived DC, moDC) and then stimulated with the patient's own cancer removed at surgery. These DCs are injected back into the patients to boost the immune system (DC Vaccination). Phase I/II trials have shown this approach is very useful in some patients, allowing patients to live significantly longer than predicted, but for many the effect is limited. More research is needed to make these promising treatments more effective in more patients. Our proposal aims is to increase the effectiveness of current DC vaccines, to test potentially even more effective DC approaches and examine combinations with other treatments that boost the immune system. We will do this this by: 1. Enhancing the function of DC by blocking specific signalling pathways: Cancer is able to suppress the immune system, and in particular can suppress the important functions of DCs. We and other have found specific signalling pathways within the DC by which cancer can do this and have shown that specific drugs can block these and restore DC function. We will apply this knowledge to improve current DC therapy against GBM. Using DC from healthy donors and GBM patients and using GBM cell lines and tumour removed at operation, we will test how well the pathway blocking drugs enhance DC function. 2. Compare circulating DC populations with the current laboratory generated moDC and test feasibility for use in vaccines: DCs circulating naturally in the blood have favourable characteristics compared to moDC, generated in the laboratory, and are potentially more potent as DC vaccines. I will test this in relation to GBM and will test whether these can be enhanced in the same way as moDC. In preliminary experiments I have shown that circulating DC are reduced in GBM patients compared to healthy people, however modern techniques allow isolation of small numbers of cells for use as vaccines. In this proposal I will test whether one can actually prepare a vaccine from circulating DCs in GBM. This is very important because, in addition to potentially being better vaccines, these DC do not need culture in a specialised laboratory and so treatments may be more accessible to more patients. 3. Combine DC therapy and Checkpoint blockade: A new class of anti cancer drugs, that 'release the brakes' on the immune system (checkpoint blockade) have shown very promising results in a range of cancers. Using experimental systems already established in our laboratories, we will combine our enhanced DCs, which 'turn on' T cells and checkpoint blockade drugs which 'take the brakes off' the T cell, and test if we can produce even more effective anti-cancer T-cells. If our experiments are successful, we expect these finding to be incorporated very quickly into the next generation of clinical trials and so potentially giving patient benefit over the next five years. This will be facilitated by our collaborators who have on going DC vaccine clinical programmes. Our aim being a treatment which prolongs survival, with little toxicity and improved quality of life for GBM patients. The ability to target DC function and so modify immnue responses has implications for other areas of immunology such as autoimmunity and infectious diseases. We also envisage that our finding can be extrapolated to other cancers with similar benefits.