#TCR REPERTOIRE DIVERSITY REVIEW TRIAL#

ICIs, which target T cells to suppress their programmed death‐1 (PD‐1) receptor and activate an anti‐tumor immune response, have brought substantial transformations in the treatment of various cancer types. In recent years, enormous progress has been made in understanding TCR diversity in immunotherapy. The majority of T cells in the human peripheral blood are made up of TCR α and β chains, while a small portion (1%‐5%) contains TCR δ and γ chains. Regarding T cells, it has been found that the T‐cell receptor (TCR) repertoire has an important impact on a wide range of disease, including malignancy, autoimmune disorders, and infectious diseases, and is involved with the immune system in almost all human health conditions and diseases. T cells are the active cell population that mediates cellular immune response and function as an essential component in humoral immune system activation response. Unified predictive model for ICI efficacy should be developed, and different components affecting the tumor‐host interactions should be considered in the development of such a model. This may be a practical choice under current technical conditions but is still insufficient for comprehensively identifying patients who would benefit from immunotherapy. Nevertheless, most of the existing studies predicting the clinical efficacy of immunocheckpoint blocking therapy (ICB) focused solely on single factors, possibly because the analyses are much easier to be conducted on single variate. Havel et al., however, found that the efficacy of ICIs might be influenced by certain factors such as tumor genomics, host germline genetics, programmed death‐ligand 1 (PD‐L1) levels, tumor microenvironment, and intestinal microbiome. Immunotherapy has nowadays developed into a new and promising therapy in addition to surgery, radiotherapy, chemotherapy, and molecular targeted therapy.

#TCR REPERTOIRE DIVERSITY REVIEW TRIAL#

In recent years, the clinical trial results of genetically engineered immune cells, including chimeric antigen receptor T‐cell (CAR‐T), TCR‐engineered T‐cell (TCR‐T), chimeric antigen receptor natural killer cell (CAR‐NK) and more, in the treatment of hematological tumors have also been encouraging. Since the year 2011, there have been rapid developments in the field of immunotherapy, and a range of immunocheckpoint inhibitors (ICIs) have been approved for a range of metastatic cancers, including malignant melanoma, lung, kidney, and bladder cancers. In conclusion, intensive studies over an extended range of cancer types and a broadened group of subjects should be carried to solidify the TCR repertoire's position as an immunotherapy biomarker. Recent progress of TCR sequencing technology in tumor research is also discussed. In this article, we reviewed TCR rearrangement mechanisms and analysis methods. The results of some studies are even contrary. Still, existing researches are insufficient to clarify the specific clinical implications of TCR dynamic change and the definite role of TCR repertoire diversity during the treatment process. Accurate delineation of the T‐cell repertoire can further the understanding of the immune system response to tumorigenesis.

The potential of TCR repertoire as a biomarker for immunotherapy efficacy is also widely studied as TCR repertoire represents different baseline within individuals and shows dynamic change during treatment. Results have shed light on the TCR repertoire differences between cancer patients and healthy control as well as between individual's lesions, paracancer, and peripheral blood samples. Based on this new methodology, discoveries are made across a range of tumor types. Nowadays, next‐generation sequencing technology allows the simultaneous detection of TCR sequences with high throughput, and several evaluation indexes facilitate the measure of TCR repertoire. Thus, TCR repertoire analysis occupied an important position in T‐cell regarding research. The unique rearrangement mechanisms during T‐cell maturation provide great diversity to TCR, ensuring specific recognition between T cells and antigens. Mature T cells can specifically recognize the antigen on the major histocompatibility complex (MHC) molecule through T‐cell receptors (TCR). T cells, which are involved in adaptive immunity, are essential in the elimination of tumor cells.

Tcr repertoire diversity review