Over the past decade, immunotherapy has revolutionized cancer treatment, improving the chance for cure and survival even for poor-prognosis tumors. Immune checkpoint inhibitors (ICIs) have been readily incorporated into standard therapeutic strategies for several early and advanced tumor settings, given the evidence of durable disease response and better quality of life. Advancements in oncology, immunology, and molecular biology research have poised the field for greater growth beyond immune checkpoint blockade. Engineered immune cells against specific tumor antigens (Chimeric antigen receptor (CAR)-T cells) represent a significant step forward in anticancer precision medicine, able to specifically identify and eliminate tumor cells, together with Tumor-infiltrating lymphocyte (TIL)-based therapy and bispecific T-cell engager molecules. The advent of stereotactic irradiation has led to increasingly precise, safe, and effective local treatments, whose radiobiological basis relies on the induction of vascular damage and immune modulation, paving the way for a synergistic regulation of cancer immunity with drugs.

The increasing complexity of cancer care calls for a multidisciplinary approach. In the modern context of personalized treatments, understanding the effect of immunotherapy on immune tolerance is essential to ensure an effective antitumor immune response with minimal, predictable, easily manageable toxicity. For instance, the efficacy of CAR-T cell therapy on solid tumors may be hindered by a hostile, hypoxic, acid, immunosuppressive tumor microenvironnent (TME), that is, the complex system of cancer cells, cytokines, stromal components and various immune cell subsets whose active role in cancer growth, invasiveness and metastatization is clearly emerging. On the other hand, radiotherapy can elicit endothelial dysfunction, driving tumor hypoxia and triggering immune cell recruitment.

This Research Topic aims to tackle cancer treatment innovation. First, exploring the biological relationship among checkpoint targets, tumor neoantigens, tumor mutational burden, tumor infiltrating lymphocytes, and cancer immunoediting, underpinning tumor response to immunotherapy. Second, a full comprehension of the dynamics of the TME is crucial for the development of targeted cancer treatments, together with the central role of immune cell metabolism in building next-generation cell therapy. Third, assessing the impact of radiation-induced tumor cell and TME modifications and their effect on cancer immune recognition.

We welcome original research papers, clinical and pre-clinical data (in-vitro and in-vivo/ex-vivo models), and systematic and narrative reviews and mini-reviews that address, but need not be limited to, new immunological insights at the molecular, cellular, or whole-organism level, such as:

--How mitochondrial and glycolytic metabolisms influence cancer cell signalling
--Antigenic profiling, genomic/radiogenomic and transcriptomic models, and/or the identification of metabolic signatures to enhance anticancer immune response and reduce off-target toxicity of radiotherapy and immunotherapy

Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases, which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo), are out of scope for this Research Topic.

Please note that Dr Lilia Bardoscia has received funding from IPSEN, JANSSEN, ASTELLAS and TEMA SINERGIE, and Dr José María Ayuso is one of the founders of Visinya Biotechnologies LLC, a start-up developing microfluidic devices for cell culture applications

Are you interested in contributing a manuscript to this Research Topic?

Cancer Immunity, Modern Radiotherapy and Immunotherapy: A Journey into Cancer Treatment Innovation