Spatial-timely Quantitative Network Analysis for TGF-β pathway of Tumor
Infiltrating Lymphocytes
Abstract
Tumor-infiltrating lymphocytes (TILs) are to be subject to clinical
applications by cultured TIL infusion in vivo for adoptive cell therapy
(ACT) and by ex vivo TIL analysis for determining immune characteristics
to kill autologous tumor cells so that TIL has been administrated
tumor’s patients to immune-cell therapy and analyze patients’ immune
characteristics for tumor diseases. To study the TIL features, we have
established quantitative network modeling by TIL’s TCR signaling
pathway, IL2 pathway, and TGF-β pathway for personalized immunotherapy
for more than fifteen years. However, machine-learning analysis still
has some challenges under the traditional quantitative pathway for
network configurations to apply for patient treatment. For example,
multiple protein complexes competing for downstream DNA binding-site or
protein-protein complex will generate different effects. To address this
question, we report here a temporal-spatial quantification network,
termed a spatial-timely quantification network, to address the
spatial-timely competition of complex proteins binding to downstream
proteins or DNA in network analysis. After studying spatial-timely
quantitative network modeling by TGF-β pathway activity in
spatial-timely order, we discover that multiple protein complexes using
spatial-timely quantitative networks are much better than traditional
quantitative networks. Once the new system modeling is established, we
can further analyze all pathways, such as the TCR signaling pathway and
IL2 pathway from TIL, for different immunotherapy.