CX3CR1 deficiency-induced TIL tumor restriction as a novel addition for CAR-T design in solid malignancies

Trinh, Thu Le; Adams, William A.; Calescibetta, Alexandra; Tu, Nhan; Dalton, Robert; So, Tina; Wei, Max; Ward, Grace A; Kostenko, Elena; Christiansen, Sean; Cen, Ling; McLemore, Amy F; Reed, Kayla; Whitting, Junmin; Gilvary, Danielle L.; Blanco, Neale Lopez; Segura, Carlos Moran; Kandell, Wendy; Chen, Xianghong; Cheng, Pingyan; Wright, Gabriëla; Cress, W. Douglas; Liu, Jinghong; Wright, Kenneth L.; Wei, Sheng; Eksioglu, Erika A.

doi:10.1016/j.isci.2023.106443

Cited by 10 publications

(4 citation statements)

References 103 publications

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“…We found that their marker genes, CX3CR1, FAM3C and DUSP4, were predictive of iCCA patients' survival. These genes are previously reported as biomarkers in several other cancer types (47)(48)(49), further supporting their prognostic values. On the other hand, it is worth noticing that these markers may not only express in Temra and terminal Tex cells.…”

Section: Discussionsupporting

confidence: 74%

Directly selecting differentially expressed genes for single-cell clustering analyses

Chen,

Wang,

Huang

et al. 2023

Preprint

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In single-cell RNA sequencing (scRNA-seq) studies, cell-types and their associated marker genes are often identified by clustering and differential expression gene (DEG) analysis. scRNA-seq data contain many genes not relevant to cell-types and gene selection procedures are needed for more accurate clustering. An ideal gene selection procedure should select all DEGs between cell-types for best cell-type identification. However, because cell-types are unknown, gene selection and DEG analysis are performed separately using different methods. Genes are selected using surrogate criteria not directly related with clustering, which often miss important genes or select unimportant genes. Clustering accuracy could be seriously influenced because of the inferior gene selection. DEGs are often detected by comparing different clusters, leading to many false DEGs due to the selection bias problem. In this paper, we present Festem, a unified method for gene selection and DEG analysis in scRNA-seq studies. Festem investigates gene's clustering information based on the observation that marginal distributions of DEGs are mixtures of their different cell-type-conditional distributions, and can directly select the clustering-informative DEGs and avoid the selection bias problem. Extensive simulation and real data analyses show that Festem achieves high precision and recall for DEG detection, and enables more accurate clustering and cell-type identification. Applications to several scRNA-seq datasets demonstrate that Festem can identify cell-types that are often missed by other methods. In a large intrahepatic cholangiocarcinoma dataset, we identify CD8+ T cell-types and find that their marker genes are novel prognostic biomarkers.

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Section: Discussionsupporting

confidence: 74%

Directly selecting differentially expressed genes for single-cell clustering analyses

Chen,

Wang,

Huang

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“… 56 We found that their marker genes, CX3CR1 , FAM3C , and DUSP4 , were predictive of survival in patients with iCCA. These genes have been previously reported as biomarkers in several other cancer types, 57 , 58 , 59 further supporting their prognostic values. On the other hand, it is worth noting that these markers may not only express in T emra and terminal T ex cells.…”

Section: Discussionsupporting

confidence: 72%

Directly selecting cell-type marker genes for single-cell clustering analyses

Chen,

Wang,

Huang

et al. 2024

Cell Reports Methods

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“…For instance, it has been showed that CAR-T cells overexpressing the IL-8 receptors CXCR1 or CXCR2 had better tumor infiltration and anti-tumor effects [ 81 ]. Other chemokine receptor targets under investigation included CX3CR1 [ 82 ], CXCR5 [ 83 ], etc. The research has indicated that CAR-T cells overexpressing chemokine receptors exhibited enhanced tumor infiltration capability and lower off-tumor, on-target toxicity.…”

Section: Challenges and Coping Strategies Of Immunosuppressive Microe...mentioning

confidence: 99%

Current challenges and therapeutic advances of CAR-T cell therapy for solid tumors

Chen,

Wang,

Chen

et al. 2024

Cancer Cell Int

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The application of chimeric antigen receptor (CAR) T cells in the management of hematological malignancies has emerged as a noteworthy therapeutic breakthrough. Nevertheless, the utilization and effectiveness of CAR-T cell therapy in solid tumors are still limited primarily because of the absence of tumor-specific target antigen, the existence of immunosuppressive tumor microenvironment, restricted T cell invasion and proliferation, and the occurrence of severe toxicity. This review explored the history of CAR-T and its latest advancements in the management of solid tumors. According to recent studies, optimizing the design of CAR-T cells, implementing logic-gated CAR-T cells and refining the delivery methods of therapeutic agents can all enhance the efficacy of CAR-T cell therapy. Furthermore, combination therapy shows promise as a way to improve the effectiveness of CAR-T cell therapy. At present, numerous clinical trials involving CAR-T cells for solid tumors are actively in progress. In conclusion, CAR-T cell therapy has both potential and challenges when it comes to treating solid tumors. As CAR-T cell therapy continues to evolve, further innovations will be devised to surmount the challenges associated with this treatment modality, ultimately leading to enhanced therapeutic response for patients suffered solid tumors.

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CX3CR1 deficiency-induced TIL tumor restriction as a novel addition for CAR-T design in solid malignancies

Cited by 10 publications

References 103 publications

Directly selecting differentially expressed genes for single-cell clustering analyses

Directly selecting differentially expressed genes for single-cell clustering analyses

Directly selecting cell-type marker genes for single-cell clustering analyses

Current challenges and therapeutic advances of CAR-T cell therapy for solid tumors

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