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. As we believe that PD-1 might be implicated in the absence of T cell arrest observed after anti CTLA-4 treatment, we treated mice with anti PD-1 antibody. We observed that, when combined to anti CTLA-4 treatment, anti PD1 strongly inhibit tumor growth. The next step is to image the behavior of TIL and determine whether they stably interact with tumor cell and induce cell death after the combined treatment.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2014
- Accession Number
- ADA603836
Entities
People
- Betty Diamond
- Helene Beuneu
- Michael Dustin
- Sandra Demaria
Organizations
- New York University