Visualizing Breast Cancer Cell Interaction with Tumor-Infiltrating Lymphocytes During Immunotherapy
Abstract
This project takes advantage of a well-characterized mouse model of metastatic breast cancer and use of two photon microscopy on live animal to observe the T cell behavior within the primary tumor and lung metastasis environment after anti-CTLA-4 treatment in presence or not of radiotherapy treatment. We transfected 4T1 tumor cells with a FRET based reporter probe of Caspase 3 activation. It allowed us to follow cell death in vitro and in vivo. We have also been able to detect cytotoxic T cells expressing Granzyme B within the tumor. These tools can now be used to dissect the cytotoxic activity of TIL after treatment. Interestingly, we have shown that the treatment with anti CTLA-4 antibody 9H10 increases expression of PD-1 on the TIL surface. This finding is of major importance and is consistent with our hypothesis that PD-1 might be implicated in the absence of T cell arrest observed after anti CTLA-4 treatment. We strongly believe that T cell stop is crucial to allow tumor cell elimination. We will then test if treating the tumor bearing mice with anti CTLA-4 and anti PD-1 will allow TIL to stably interact with tumor cell and induce cell death.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2013
- Accession Number
- ADA577265
Entities
People
- Helene Beuneu
- Michael Dustin
- Sandra Demaria
Organizations
- New York University