Joint Call (JTC 2021)

Aim 1: Identification and validation of TME subclasses and their contribution to the resistance mechanisms: Translational research using tumour samples collected from retrospective and/or prospective cohorts of patients.

1.1 Dissection of tumour cells/tumour-infiltrating immune/stromal cells and identification of TME subclasses (single-cell analyses, mass cytometry, imaging, multidimensional immunohistochemistry, etc.) for TME studies (3D culture systems; patient-derived organoids; patient-derived xenografts; syngeneic, genetically modified and chemical carcinogenesis-induced mouse models, etc.).

1.2 Definition of the contribution of TME to resistance mechanisms and identification of new therapeutic targets through multiomics (epigenomic, transcriptomic, proteomic, metabolomics, study of the microbiome and virome, etc.) to assess functional characteristics of TME-tumour cell interplay within the primary tumour and/or metastases (e.g the underlying signaling, the transcriptional landscape, the cell-cell communication, the network regulation of immune cells, etc.), to identify candidate TME targets and to assess the activity of pathway-targeting agents.

1.3 Development of tools capable of predicting treatment efficacy and tumour recurrence using minimally- or noninvasive techniques (generation of algorithms modelling the network dynamics, predictive models based on artificial intelligence, integrating -omics data and network approaches).

Development of robust noninvasive biomarkers of disease course (radiomics, cell-free circulating tumour DNA, miRNA signatures, circulating tumour cells, etc.).

Sex/gender impact must be considered.

Aim 2: Identification and validation of TME subclasses and their contribution to the resistance mechanisms: Translational research using tumour samples collected from retrospective and/or prospective cohorts of patients.

2.1 Development of new precision therapeutic strategies that may prevent human tumour recurrence or resistance (T-cell-based cancer immunotherapies, immune checkpoint blockers (ICBs), chimeric antigen receptor (CAR)-T-cells, preventive and therapeutic vaccines, etc.).

2.2 Evaluation in translational studies of the impact of TME on treatment efficacy and patient outcome (clinical utility of specific TME feature detections or identifications, clinical utility of specific intratumour or peripheral blood immune biomarkers, sex/gender impact, etc.).

2.3 Phase I and II clinical trials (combinations of available treatments, new therapeutic strategies, new administration schemes, etc.) targeting, or preventing resistance of multiple TME features.

Particular attention should be given to gender balance inclusion in order to intercept sex/gender differences and to determine if there is an association between sex/gender and treatment response.