scholarly journals Individual cell‐based modeling of tumor cell plasticity‐induced immune escape after CAR‐T therapy

2021 ◽  
Vol 1 (3) ◽  
Author(s):  
Can Zhang ◽  
Changrong Shao ◽  
Xiaopei Jiao ◽  
Yue Bai ◽  
Miao Li ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Immune Escape ◽  
Individual Cell ◽  
Cell Plasticity ◽  
Tumor Cell Plasticity ◽  
Car T

scholarly journals Individual cell-based modeling of tumor cell plasticity-induced immune escape after CAR-T therapy

2020 ◽  
Author(s):  
Can Zhang ◽  
Changrong Shao ◽  
Xiaopei Jiao ◽  
Yue Bai ◽  
Miao Li ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Cell ◽  
Computational Model ◽  
B Cell ◽  
Individual Cell ◽  
Cell Plasticity ◽  
Model Framework ◽  
Tumor Relapse ◽  
Tumor Cell Plasticity ◽  
Car T

AbstractChimeric antigen receptor (CAR) therapy targeting CD19 is an effective treatment for refractory B cell malignancies, especially B cell acute lymphoblastic leukemia (B-ALL). The majority of patients achieve a complete response following a single infusion of CD19-targeted CAR-modified T cells (CAR-19 T cells); however, many patients suffer relapse after therapy, and the underlying mechanism remains unclear. To better understand the mechanism of tumor relapse, we developed an individual cell based computational model for tumor cell plasticity and the heterogeneous responses to the CAR-T treatment. Model simulations reproduced the process of tumor relapse, and predicted that CAR-T stress-induced cell plasticity can lead to tumor relapse in B-ALL. Model predictions were verified by applying the second-generation CAR-T cells to mice injected with NALM-6-GL leukemic cells, in which 60% of the mice relapse within 3 months, and relapsed tumors retained CD19 expression but exhibited a subpopulation of cells with CD34 transcription. These findings lead to a mechanism of tumor replace by which CAR-T treatment induced tumor cells to transition to hematopoietic stem-like cells (HSLCs) and myeloid-like cells and hence escape of CAR-T targeting. The computational model framework was successfully developed to recapitulate the individual evolutionary dynamics, which could predict clinical survival outcomes in B-ALL patients after CAR-T therapy.

scholarly journals The Intimate Relationship among EMT, MET and TME: A T(ransdifferentiation) E(nhancing) M(ix) to Be Exploited for Therapeutic Purposes

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3674 ◽  
Author(s):  
Ralf Hass ◽  
Juliane von der Ohe ◽  
Hendrik Ungefroren
Keyword(s):  
Stem Cell ◽  
Phenotypic Plasticity ◽  
Tumor Cell ◽  
Epithelial Mesenchymal Transition ◽  
Resistance Mechanisms ◽  
Current Evidence ◽  
Cell Plasticity ◽  
New Paradigm ◽  
Mesenchymal Transition ◽  
Tumor Cell Plasticity

Intratumoral heterogeneity is considered the major cause of drug unresponsiveness in cancer and accumulating evidence implicates non-mutational resistance mechanisms rather than genetic mutations in its development. These non-mutational processes are largely driven by phenotypic plasticity, which is defined as the ability of a cell to reprogram and change its identity (phenotype switching). Tumor cell plasticity is characterized by the reactivation of developmental programs that are closely correlated with the acquisition of cancer stem cell properties and an enhanced potential for retrodifferentiation or transdifferentiation. A well-studied mechanism of phenotypic plasticity is the epithelial-mesenchymal transition (EMT). Current evidence suggests a complex interplay between EMT, genetic and epigenetic alterations, and clues from the tumor microenvironment in cell reprogramming. A deeper understanding of the connections between stem cell, epithelial–mesenchymal, and tumor-associated reprogramming events is crucial to develop novel therapies that mitigate cell plasticity and minimize the evolution of tumor heterogeneity, and hence drug resistance. Alternatively, vulnerabilities exposed by tumor cells when residing in a plastic or stem-like state may be exploited therapeutically, i.e., by converting them into less aggressive or even postmitotic cells. Tumor cell plasticity thus presents a new paradigm for understanding a cancer’s resistance to therapy and deciphering its underlying mechanisms.

scholarly journals Tumor cell plasticity: the challenge to catch a moving target

2014 ◽  
Vol 49 (4) ◽  
pp. 618-627 ◽  
Author(s):  
Sarah Schwitalla
Keyword(s):  
Tumor Cell ◽  
Moving Target ◽  
Cell Plasticity ◽  
Tumor Cell Plasticity

Functional role of matrix metalloproteinases in ovarian tumor cell plasticity

2004 ◽  
Vol 190 (4) ◽  
pp. 899-909 ◽  
Author(s):  
Anil K. Sood ◽  
Mavis S. Fletcher ◽  
Jeremy E. Coffin ◽  
Maria Yang ◽  
Elisabeth A. Seftor ◽  
...  
Keyword(s):  
Matrix Metalloproteinases ◽  
Tumor Cell ◽  
Ovarian Tumor ◽  
Functional Role ◽  
Cell Plasticity ◽  
Ovarian Tumor Cell ◽  
Tumor Cell Plasticity

The Role of Axl Receptor Tyrosine Kinase in Tumor Cell Plasticity and Therapy Resistance

2017 ◽  
pp. 351-376 ◽  
Author(s):  
Kjersti T. Davidsen ◽  
Gry S. Haaland ◽  
Maria K. Lie ◽  
James B. Lorens ◽  
Agnete S. T. Engelsen
Keyword(s):  
Tyrosine Kinase ◽  
Tumor Cell ◽  
Receptor Tyrosine Kinase ◽  
Therapy Resistance ◽  
Cell Plasticity ◽  
Tumor Cell Plasticity ◽  
Axl Receptor Tyrosine Kinase

Prostatic tumor cell plasticity involves cooperative interactions of distinct phenotypic subpopulations: Role in vasculogenic mimicry

The Prostate ◽  
2002 ◽  
Vol 50 (3) ◽  
pp. 189-201 ◽  
Author(s):  
Navesh Sharma ◽  
Richard E.B. Seftor ◽  
Elisabeth A. Seftor ◽  
Lynn M. Gruman ◽  
Paul M. Heidger ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Vasculogenic Mimicry ◽  
Cell Plasticity ◽  
Cooperative Interactions ◽  
Tumor Cell Plasticity ◽  
Prostatic Tumor

scholarly journals Tumor cell plasticity: vascularisation beyond angiogenesis

2008 ◽  
Author(s):  
F. Hillen
Keyword(s):  
Tumor Cell ◽  
Cell Plasticity ◽  
Tumor Cell Plasticity
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