2/18/2024 0 Comments Tcr repertoire profilingThe roles of T cells in the TME and CIT are multiple. T cells are the main component of lymphocytes and play an essential part in the immune response through cellular contacts or the killer cytokines’ secretion, serving as the body’s fighters against disease, infection and tumor formation. Meanwhile, this review also includes exploring RT combined with immunotherapy as a potential cancer treatment strategy. This review provides insight into radiation therapy’s immunomodulatory and remodeling effects on the TME, including immune cells and non-cellular components. Therefore, RT is early included in the category of combined immunotherapy research. At the same time, RT triggers the expression and presentation of pre-existing and specific neoantigens in tumor cells, increasing immunogenicity. The resulting inflammatory signaling effect remodels the TME. Radiotherapy (RT) induces micronuclei in tumor cells to activate cytoplasmic nucleic acid sensors, further activating the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway and the expression of type I interferon (IFN-I). To maximize the therapeutic effect, the combination of immunotherapy with other therapeutic approaches has gradually gained attention. The implementation of CIT requires a thorough understanding of the interaction between the tumor and the immune system and the intricate regulatory networks in the tumor microenvironment (TME). Although immunotherapy has demonstrated significant efficacy in clinical applications, only a small proportion of patients benefit, with an objective response rate of 10–30%. Currently, the most widely studied and applied immunotherapy is ICB targeting immune checkpoint (IC) molecules such as programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4). This strategy includes immune checkpoint blockade (ICB), adoptive cell therapy (ACT), cancer vaccines, and other approaches that target specific molecules or pathways involved in immune suppression or activation. This treatment has shown unprecedented response in patients and brought hope to many cancer patients. Similar content being viewed by othersĬancer immunotherapy (CIT) is a treatment method that stimulates the immune system to attack and suppress tumor development, including promoting immune activation and relieving immune suppression. In addition, we discuss the impact of different RT modalities on tumor immunity and issues related to the clinical practice of combination therapy. Meanwhile, non-cellular components such as lactate and extracellular vesicles are also elaborated. In this review, we summarize the effects of RT on cellular components of the TME, including T cell receptor repertoires, different T cell subsets, metabolism, tumor-associated macrophages and other myeloid cells (dendritic cells, myeloid-derived suppressor cells, neutrophils and eosinophils). Therefore, the combination of RT and immunotherapy is expected to achieve improved efficacy. Radiotherapy (RT) not only kills tumor cells but also triggers the pro-inflammatory molecules’ release and immune cell infiltration, which remodel the tumor microenvironment (TME). ![]() A synergistic anti-tumor response may be produced through the combined application with traditional tumor treatment methods. However, immunotherapy has minimal benefit for patients in most types of cancer and is largely ineffective in some cancers (such as pancreatic cancer and glioma). Cancer immunotherapy has transformed traditional treatments, with immune checkpoint blockade being particularly prominent.
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