Human Tumour Microenvironment Immunoprofiling The ultimate aim and core activity is to create a database containing integrated cellular and molecular data from the tumour microenvironment of patients treated with both targeted and non-targeted therapy, in particular immunotherapy, as well as key information from patient history and clinical progression. Core activity (broad profiling): development of a fully integrated data set of defined immune cell subsets (deliverables (1) and (2)) in samples from patients from specific cancer indications treated with radiotherapy, chemotherapy, targeted therapy and, in particular, targeted immune checkpoint therapy and correlation to the oncogenomic profile of the tumour.Supplemental activities:in-depth profiling of a subset of samples from patients undergoing immunotherapy using selected advanced technologies;development of a sustainable open-access, royalty-free and precompetitive database that houses such a data set, including the required privacy settings;generation of a biomarker validation platform to identify and start to characterise potential predictive biomarkers for single-agent and combinatorial immunotherapy trials. To improve therapy, the understanding of the tumour microenvironment needs to evolve. Firstly, the understanding of tumour/host interaction on the cellular and molecular level in the absence of therapeutic intervention needs to improve. Both individual tumours and individual hosts are heterogeneous with respect to the quality and degree of immunity. Understanding the cellular and molecular nature of the tumour microenvironment will (i) help us characterise the ability of a patient’s immune system to mount an anti-tumour attack and (ii) provide ideas which pharmacological interventions may support or activate the immune cells to attack the tumour cells.Secondly and in close alignment with the previous paragraph, one needs to understand how current therapeutic approaches affect the host/tumour interaction to have a baseline from which to improve the current therapeutic paradigm. Such data could be used to further improve currently available treatments or to develop new potential therapeutic strategies. The proposed topic, for the first time, will assemble a consortium to generate a data set sufficient to gain a meaningful view of the tumour micro-environment. The generation of such a data set is the core activity of this IMI2 JU topic while the future purposes (improvement of the currently available treatments and development of potential therapeutic strategies) go beyond the frame of this topic. A comprehensive database, profiling immune cells in the tumour microenvironment (TME) of patients that are responsive to immune checkpoint blockade versus those that are not, is generally lacking at the present time and therefore the creation of such a database is the ultimate aim of this IMI2 JU topic. A searchable database, with integrated tumour genomic information along with matched immune profiles and (immune) therapy outcome, will enable users to identify biological networks involved in, and develop biomarkers to predict response to, immunotherapy. Maximum impact would be achieved by continued integration of clinical outcome data received after the end of the consortium. This IMI2 JU topic is expected to be the basis for future significant impacts but these will go beyond the scope and timeframe of the IMI2 JU topic:identification of novel predictive biomarkers and patient selection strategies and thereby improving clinical response rate to current cancer immunotherapy and other therapeutic regimens in oncology; such discoveries and improvements should enhance clinical and healthcare practice; understanding mechanism(s) of resistance to current immunotherapy, but also other therapy regimens, to enable identification of new therapeutic targets;establishing rational combination immunotherapy strategy (this should strengthen competitiveness and help to address the specific societal challenge of low response rates in cancer patients to current therapies);deriving therapy solutions for patients that are insensitive to immune checkpoint blockade (thus generating a positive impact on European cancer patients’ health and wellbeing in the long-term);understanding molecular effects and potential safety liability of immunotherapy.