scholarly journals Single Cell Transcriptome in Colorectal Cancer—Current Updates on Its Application in Metastasis, Chemoresistance and the Roles of Circulating Tumor Cells

2020 ◽  
Vol 11 ◽  
Author(s):  
Francis Yew Fu Tieng ◽  
Rashidah Baharudin ◽  
Nadiah Abu ◽  
Ryia-Illani Mohd Yunos ◽  
Learn-Han Lee ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Single Cell ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

Morphologic and genomic characterization of circulating tumor cells in patients with metastatic colorectal cancer treated with combinational treatment of andecaliximab, bevacizumab and chemotherapy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14753-e14753
Author(s):  
Stephanie Shishido ◽  
Peter Kuhn
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Single Cell ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Liquid Biopsy ◽  
Clinical Decision Making ◽  
Line Therapy ◽  
Combinational Treatment

e14753 Background: The liquid biopsy is a noninvasive route to evaluate circulating tumor cells (CTCs) during the course of treatment to gain understanding of tumor biology, with potential prognostic utility. CTCs could serve as a predictive biomarker while aiding in the identification of resistance mechanisms to treatment through single cell genomic and proteomic analysis providing a longitudinal snapshots of tumor heterogeneity. Methods: Through the use of the high definition single cell assay (HD-SCA) workflow, we characterized the rare circulating cells to determine prognostic value of the liquid biopsy in monitoring the efficacy of andecaliximab in a combinational treatment as 1st or 2nd line therapy in patients with metastatic colorectal cancer (mCRC). 174 samples from 95 patients were analyzed to determine the significance of CTCs during treatment. Results: HD-CTCs were detected in 31% of samples, with 41 (43%) patients being CTC positive in at least 1 timepoint during the study. Patients receiving 1st line therapy presented with a median of 0 (range 0-346.04) and a mean of 9.49 (±14.06) HD-CTC/mL at baseline (BL). At initiation of 2nd line therapy, patients presented with a median of 0 HD-CTC/mL (range 0-277.37) and a mean of 10.94 (±15.32). There was no association between BL HD-CTC/mL and response, but for the 20 patients with > 1 HD-CTC at BL, there was a trend toward response for higher HD-CTC/mL (non-response: mean 2.8, n = 12; response: mean 89.7, n = 8; p = .04). The 3 patients with > 10 HD-CTC/mL at BL had undetectable HD-CTC on-treatment, which accompanied radiologic partial response; however, the 2 patients with complete radiological response had no HD-CTC detected at BL. In case studies, treatment pressure led to an observable change in HD-CTC morphology and genomic instability (single cell CNV analysis), suggesting these parameters may inform prognosis. Conclusions: Characterization of CTCs from patients with mCRC is feasible and may provide prognostic information to guide clinical decision making. Further evaluation of CTCs for pharmacodynamics and clinical monitoring in patients with mCRC is warranted.

scholarly journals Single-cell transcriptome analysis of the immunosuppressive effect of differential expression of tumor PD-L1 on responding TCR-T cells

2020 ◽  
Author(s):  
Renpeng Ding ◽  
Shang Liu ◽  
Shanshan Wang ◽  
Huanyi Chen ◽  
Fei Wang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Single Cell ◽  
Tumor Cells ◽  
Cell Function ◽  
Immune Cell ◽  
Gene Clusters ◽  
Cellular Assays ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

AbstractPD-L1 expression levels in tumors do not consistently predict cancer patients’ response to PD-(L)1 inhibitors. We therefore evaluated how tumor PD-L1 levels affect the anti-PD-(L)1 efficacy and T cell function. We used MART-1-specific TCR-T cells (TCR-TMART-1) stimulated with MART-127-35 peptide-loaded MEL-526 tumor cells with different proportions of them expressing PD-L1 to perform cellular assays and high-throughput single-cell RNA sequencing. Compared to control T cells, TCR-TMART-1 were more sensitive to exhaustion and secreted lower pro-inflammatory but higher anti-inflammatory cytokines with increasing proportions of PD-L1+ tumor cells. The colocalization of T cells and tumor cells in gene clusters correlated negatively with the proportion of PD-L1+ tumor cells and positively with immune cell cytotoxicity. Moreover, elevated proportion of PD-L1+ tumor cells increased PD-L1 expression and decreased PD-1 expression on T cells and enhanced T cell death. The expression of PD-1 and PD-L1 in T cells and macrophages also correlated positively with COVID-19 severity.

scholarly journals Repurposing CAR targets in solid tumors via a pan-cancer single-cell transcriptome analysis

2021 ◽  
Author(s):  
Sanna Madan ◽  
Alejandro A. Schaffer ◽  
Eytan Ruppin
Keyword(s):  
Single Cell ◽  
Solid Tumors ◽  
Tumor Cells ◽  
Solid Cancer ◽  
T Cell Therapy ◽  
Promising Tool ◽  
Car T Cell Therapy ◽  
Cell Transcriptome ◽  
Tumor Types ◽  
Single Cell Transcriptome

Chimeric antigen receptor (CAR) T cell therapy is a powerful and promising tool for unleashing lasting antitumor immunity, which is currently studied in numerous blood and solid cancers. Here, mining single cell transcriptomics datasets of solid tumors, we survey many existing CAR targets, aiming to new solid tumor types in which these targets are differentially expressed in tumor cells and not on non-tumor cells within the tumor microenvironment, thus providing new repurposing opportunities. Quite surprisingly, we find that many existing solid cancer CAR targets have a better discriminatory power in uncharted cancer types than in the ones they have been developed or being tested for. Furthermore, we show that several existing liquid cancer CAR targets may also hold promise in specific solid tumors. Taken together, this analysis uncovers a large potential of repurposing current CARs that is currently yet untapped.

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