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Due to its slow progression and susceptibility to radical forms of treatment, low-grade PC is associated with high overall survival (OS). With the clinical progression of PC, the therapy is becoming more complex. The immunosuppressive tumor microenvironment (TME) makes PC a difficult target for most immunotherapeutics. Its general immune resistance is established by e.g., immune evasion through Treg cells, synthesis of immunosuppressive mediators, and the defective expression of surface neoantigens. The success of sipuleucel-T in clinical trials initiated several other clinical studies that specifically target the immune escape of tumors and eliminate the immunosuppressive properties of the TME. In the settings of PC treatment, this can be commonly achieved with radiation therapy (RT). In addition, focal therapies usually applied for localized PC, such as high-intensity focused ultrasound (HIFU) therapy, cryotherapy, photodynamic therapy (PDT), and irreversible electroporation (IRE) were shown to boost the anti-cancer response. Nevertheless, the present guidelines restrict their application to the context of a clinical trial or a prospective cohort study. This review explains how RT and focal therapies enhance the immune response. We also provide data supporting the combination of RT and focal treatments with immune therapies. [ABSTRACT FROM AUTHOR]

The tumor microenvironment (TME) has a central role in restraining tumor growth, and a deep understanding of the interplay between cancer cells and their local environment is relevant to designing immunotherapies that fit each tumor best. Today, treatment allocation of PDAC patient is currently based on clinical, biochemical, and radiologic features but, to reach a personalized treatment, it is mandatory to identify new tools to predict tumor response and develop a more effective patient treatment. Activation of tumor-specific CD8 T cells that mediate regression of the irradiated tumor as well as a non-irradiated synchronous tumor (abscopal effect) is seen only when radiation is combined with CTLA-4 blockade, whereas each treatment alone was ineffective, demonstrating a therapeutic synergy of radiation and CTLA4 blockade. Keywords: Immunotherapy; Cancer vaccines; Checkpoint blockade agents; Adoptive immunotherapy; Targeted therapies; NIBIT EN Immunotherapy Cancer vaccines Checkpoint blockade agents Adoptive immunotherapy Targeted therapies NIBIT 1777 1786 10 06/15/22 20220701 NES 220701 Introduction Oncology embrace Immunology: the way forward captioned the XVII international meeting of the Italian Network for Tumor Biotherapy (NIBIT) held in Verona on October 11-13, 2019. [Extracted from the article]

The field of cancer therapy has undergone a major transformation in less than a decade due to the introduction of checkpoint inhibitors, the advent of next generation sequencing and the discovery of neoantigens. The key observation that the breadth of each patient's immune response to the unique mutations or neoantigens present in their tumor is directly related to their survival has led oncologists to focus on driving immune responses to neoantigens through vaccination. Oncology has entered the era of precision immunotherapy, and cancer vaccine development is undergoing a paradigm shift. Neoantigens are short peptide sequences found in tumors, but not noncancerous tissues, the vast majority of which are unique to each patient. In addition to providing a description of the distinguishing features of neoantigen discovery platforms, this review will address cross-cutting personalized cancer vaccine design themes and developmental stumbling blocks. Immunoinformatic pipelines that can rapidly scan cancer genomes and identify 'the best' neoantigens are in high demand. Despite the need for such tools, immunoinformatic methods for identifying neoepitopes in cancer genomes are diverse and have not been well-validated. Validation of 'personalized vaccine design pipelines' will bring about a revolution in neoantigen-based vaccine design and delivery. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) are the dominant class of antigen-presenting cells in humans; therefore, a range of DC-based approaches have been established to promote an immune response against cancer cells. The efficacy of DC-based immunotherapeutic approaches is markedly affected by the immunosuppressive factors related to the tumor microenvironment, such as adenosine. In this paper, based on immunological theories and experimental data, a hybrid model is designed that offers some insights into the effects of DC-based immunotherapy combined with adenosine inhibition. The model combines an individual-based model for describing tumor-immune system interactions with a set of ordinary differential equations for adenosine modeling. Computational simulations of the proposed model clarify the conditions for the onset of a successful immune response against cancer cells. Global and local sensitivity analysis of the model highlights the importance of adenosine blockage for strengthening effector cells. The model is used to determine the most effective suppressive mechanism caused by adenosine, proper vaccination time, and the appropriate time interval between injections. [Display omitted] • We propose a hybrid model to describe the immunosuppressive function of adenosine in tumor micro environment. • Our model provides immunologists with a new level of insight into the role of immunosuppressive factors of the immune system. • Our model highlights the importance of adenosine blockage for strengthening effector cells and suppressing Treg cells. • Model simulations are compatible with in vivo experimental data. • The results reveals that the appropriate time interval for administration of adenosine inhibitor is between 2 and 4 days. [ABSTRACT FROM AUTHOR]