scholarly journals Evolution and characterization of carboplatin resistance at single cell resolution

2017 ◽  
Author(s):  
Devora Champa ◽  
Si Sun ◽  
Cheng-Yu Tsai ◽  
Stephen B. Howell ◽  
Olivier Harismendy

AbstractAcquired resistance to carboplatin is a major obstacle to the cure of ovarian cancer, but its molecular underpinnings are still poorly defined. We selected multiple clones derived from a single cell in parallel for similar levels of resistance to carboplatin. The resistant clones showed no significant genetic alterations, but each one activated different mechanisms of resistance resulting in transcriptional heterogeneity. Single-cell mRNA sequencing defined multiple transcriptional states associated with clone identity and resistance evolution, and identified a subset of unselected parental cells that were already in a resistant state. Six expression signatures derived from the resistant states distinguished primary from recurrent high-grade serous ovarian cancers, predicted both response and survival and disclosed functional differences between intrinsic and acquired resistance. This multidimensional, single-cell analysis offers new insights into the dynamics of the acquisition of resistance to carboplatin, a drug of major importance to the treatment of ovarian and other cancers.

2021 ◽  
Vol MA2021-01 (60) ◽  
pp. 1603-1603
Author(s):  
Sajjad Janfaza ◽  
Seyedehhamideh Razavi ◽  
Arash Dalili ◽  
Mina Hoorfar

2021 ◽  
Vol 12 ◽  
Author(s):  
Trine Sundebo Meldgaard ◽  
Fabiola Blengio ◽  
Denise Maffione ◽  
Chiara Sammicheli ◽  
Simona Tavarini ◽  
...  

CD8+ T cells play a key role in mediating protective immunity after immune challenges such as infection or vaccination. Several subsets of differentiated CD8+ T cells have been identified, however, a deeper understanding of the molecular mechanism that underlies T-cell differentiation is lacking. Conventional approaches to the study of immune responses are typically limited to the analysis of bulk groups of cells that mask the cells’ heterogeneity (RNA-seq, microarray) and to the assessment of a relatively limited number of biomarkers that can be evaluated simultaneously at the population level (flow and mass cytometry). Single-cell analysis, on the other hand, represents a possible alternative that enables a deeper characterization of the underlying cellular heterogeneity. In this study, a murine model was used to characterize immunodominant hemagglutinin (HA533-541)-specific CD8+ T-cell responses to nucleic- and protein-based influenza vaccine candidates, using single-cell sorting followed by transcriptomic analysis. Investigation of single-cell gene expression profiles enabled the discovery of unique subsets of CD8+ T cells that co-expressed cytotoxic genes after vaccination. Moreover, this method enabled the characterization of antigen specific CD8+ T cells that were previously undetected. Single-cell transcriptome profiling has the potential to allow for qualitative discrimination of cells, which could lead to novel insights on biological pathways involved in cellular responses. This approach could be further validated and allow for more informed decision making in preclinical and clinical settings.


Author(s):  
Xueqi Yan ◽  
Yinghong Xie ◽  
Fan Yang ◽  
Yijia Hua ◽  
Tianyu Zeng ◽  
...  

AbstractBreast cancer is a heterogeneous disease with a complex microenvironment consisting of tumor cells, immune cells, fibroblasts and vascular cells. These cancer-associated cells shape the tumor microenvironment (TME) and influence the progression of breast cancer and the therapeutic responses in patients. The exact composition of the intra-tumoral cells is mixed as the highly heterogeneous and dynamic nature of the TME. Recent advances in single-cell technologies such as single-cell DNA sequencing (scDNA-seq), single-cell RNA sequencing (scRNA-seq) and mass cytometry have provided new insights into the phenotypic and functional diversity of tumor-infiltrating cells in breast cancer. In this review, we have outlined the recent progress in single-cell characterization of breast tumor ecosystems, and summarized the phenotypic diversity of intra-tumoral cells and their potential prognostic relevance.


2017 ◽  
Author(s):  
Camila Egidio ◽  
Robert Durruthy-Durruthy ◽  
Michael Gonzales ◽  
Manisha Ray ◽  
Jason McKinney

Blood ◽  
2017 ◽  
Vol 130 (1) ◽  
pp. 48-58 ◽  
Author(s):  
Catherine C. Smith ◽  
Amy Paguirigan ◽  
Grace R. Jeschke ◽  
Kimberly C. Lin ◽  
Evan Massi ◽  
...  

Key Points Polyclonal mechanisms of resistance, demonstrated by single-cell analysis, occur in the majority of AML patients who relapse on quizartinib.


Sign in / Sign up

Export Citation Format

Share Document