通讯机构：
[Zhixiong Liu; Quan Cheng] D;Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China<&wdkj&>National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China<&wdkj&>Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China<&wdkj&>National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
摘要：
Chimeric antigen receptor (CAR) T cell (CAR-T cell) therapy based on gene editing technology represents a significant breakthrough in personalized immunotherapy for human cancer. This strategy uses genetic modification to enable T cells to target tumor-specific antigens, attack specific cancer cells, and bypass tumor cell apoptosis avoidance mechanisms to some extent. This method has been extensively used to treat hematologic diseases, but the therapeutic effect in solid tumors is not ideal. Tumor antigen escape, treatment-related toxicity, and the immunosuppressive tumor microenvironment (TME) limit their use of it. Target selection is the most critical aspect in determining the prognosis of patients receiving this treatment. This review provides a comprehensive summary of all therapeutic targets used in the clinic or shown promising potential. We summarize CAR-T cell therapies’ clinical trials, applications, research frontiers, and limitations in treating different cancers. We also explore coping strategies when encountering sub-optimal tumor-associated antigens (TAA) or TAA loss. Moreover, the importance of CAR-T cell therapy in cancer immunotherapy is emphasized.
摘要：
ObjectiveIn this study, we aimed to characterize the plasma metabolic profiles of brain atrophy and alcohol dependence (s) and to identify the underlying pathogenesis of brain atrophy related to alcohol dependence. MethodsWe acquired the plasma samples of alcohol-dependent patients and performed non-targeted metabolomic profiling analysis to identify alterations of key metabolites in the plasma of BA-ADPs. Machine learning algorithms and bioinformatic analysis were also used to identify predictive biomarkers and investigate their possible roles in brain atrophy related to alcohol dependence. ResultsA total of 26 plasma metabolites were significantly altered in the BA-ADPs group when compared with a group featuring alcohol-dependent patients without brain atrophy (NBA-ADPs). Nine of these differential metabolites were further identified as potential biomarkers for BA-ADPs. Receiver operating characteristic curves demonstrated that these potential biomarkers exhibited good sensitivity and specificity for distinguishing BA-ADPs from NBA-ADPs. Moreover, metabolic pathway analysis suggested that glycerophospholipid metabolism may be highly involved in the pathogenesis of alcohol-induced brain atrophy. ConclusionThis plasma metabolomic study provides a valuable resource for enhancing our understanding of alcohol-induced brain atrophy and offers potential targets for therapeutic intervention.
作者机构：
[Xu, Huilan; Tang, Kun] Cent South Univ, Xiangya Sch Publ Hlth, Dept Social Med & Hlth Management, Changsha 410008, Peoples R China.;[Tang, Kun] Cent South Univ, Xiangya Hosp, Dept Discipline Construct, Changsha 410008, Peoples R China.;[Zhang, Jingwei; Wang, Zeyu; Zhang, Hao; Zhang, Xun; Cheng, Quan; Xiao, Gelei] Cent South Univ, Xiangya Hosp, Dept Neurosurg, Changsha 410008, Peoples R China.;[Zhang, Jingwei; Wang, Zeyu; Zhang, Hao; Zhang, Xun; Cheng, Quan; Xiao, Gelei] Natl Clin Res Ctr Geriatr Disorders, Changsha 410008, Peoples R China.;[Cao, Hui] Second Peoples Hosp Hunan Prov, Brain Hosp Hunan Prov, Changsha 410007, Peoples R China.
通讯机构：
[Quan Cheng; Huilan Xu] D;Department of Social Medicine and Health Management, Xiangya School of Public Health, Central South University, Changsha 410008, China<&wdkj&>remove Hide full affiliation list<&wdkj&>Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, China<&wdkj&>National Clinical Research Center for Geriatric Disorders, Changsha 410008, China<&wdkj&>Clinical Diagnosis and Therapy Center for Glioma of Xiangya Hospital, Central South University, Changsha 410008, China<&wdkj&>Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China<&wdkj&>remove Hide full affiliation list
摘要：
Abstract: Simple Summary Immunotherapy targeting immune checkpoints and stromal cells in the tumor microenvironment is currently one of the most promising directions for tumor therapy. Ongoing studies suggest that CD73 plays an important role in the tumor immune process in certain tumors, however, the exact mechanism is unknown. We aim to fully reveal the prognostic value of CD73 in pan-cancer and its role in tumor immunity through large-scale single-cell and bulk sequencing analysis. We found that high CD73 expression was significantly associated with poor prognosis in many tumors. It is also strongly associated with immune scores, stromal cell infiltration, and immune-related pathways. CD73 can regulate the biological behavior of immune cells in the tumor microenvironment, especially macrophages and T cells. Immunotherapy targeting CD73 has obvious effects, and CD73 may shine as a new immune checkpoint in future tumor immunotherapy. Abstract CD73 is essential in promoting tumor growth by prohibiting anti-tumor immunity in many cancer types. While the mechanism remains largely unknown, our paper comprehensively confirmed the onco-immunological characteristics of CD73 in the tumor microenvironment (TME) of pan-cancer. This paper explored the expression pattern, mutational profile, prognostic value, tumor immune infiltration, and response to immunotherapy of CD73 in a continuous cohort of cancers through various computational tools. The co-expression of CD73 on cancer cells, immune cells, and stromal cells in the TME was also detected. Especially, we examined the correlation between CD73 and CD8+ (a marker of T cell), CD68+ (a marker of macrophage), and CD163+ (a marker of M2 macrophage) cells using multiplex immunofluorescence staining of tissue microarrays. CD73 expression is significantly associated with a patient’s prognosis and could be a promising predictor of these cancers. High CD73 levels are strongly linked to immune infiltrations, neoantigens, and immune checkpoint expression in the TME. In particular, enrichment signaling pathway analysis demonstrated that CD73 was obviously related to activation pathways of immune cells, including T cells, macrophages, and cancer-associated fibroblasts (CAFs). Meanwhile, single-cell sequencing algorithms found that CD73 is predominantly co-expressed on cancer cells, CAFs, M2 macrophages, and T cells in several cancers. In addition, we explored the cellular communication among 14 cell types in glioblastoma (GBM) based on CD73 expression. Based on the expression of CD73 as well as macrophage and T cell markers, we predicted the methylation and enrichment pathways of these markers in pan-cancer. Furthermore, a lot of therapeutic molecules sensitive to these markers were predicted. Finally, potential anticancer inhibitors, immunotherapies, and gene therapy responses targeting CD73 were identified from a series of immunotherapy cohorts. CD73 is closely linked to clinical prognosis and immune infiltration in many cancers. Targeting CD73-dependent signaling pathways may be a promising therapeutic strategy for future tumor immunotherapy. Keywords: CD73; cancer; immunotherapy; macrophages; T cells
