Periodic Reporting for period 1 - Hepatocarcinoma IVM (Spatiotemporal dynamics of CD8+ T cell responses to hepatocellular carcinoma)
Reporting period: 2017-07-01 to 2019-06-30
Using the multiphoton intravital microscopy (MPIVM) technique present in our BLS-3 animal facility, we could assessed the spatiotemporal dynamics of the tumor specific lymphocytes injected in HCC-bearing mice surgically prepared for liver MPIVM. We observed that the tumor specific lymphocytes displayed a more static and slow migratory behavior once they accumulate in the HCC lesions, compared to the control cells that maintain a motile phenotype. This behavior is possibly due to the cell recognition of the oncogene antigen expressed by the tumor mass since the tumor specific lymphocytes get activated, they produce IFN-γ and they increase their PD-1 and CD25 levels, indicating an activated state. Moreover they exert their cytotoxic function by inducing Caspase 3 in HCC lesions. We were able to obtain an imaging platform to study HCC in living animals and we presented our results in National and International Congresses and well as involving in the project 2 students for their master thesis.
Our study can understand how the immune system control the HCC growth, where and how it fails to respond, opening new possible therapeutic approaches in a disease that has a poor survival rate. Our study can determine new diagnostic markers that could be used by clinicians to diagnose HCC in the early phase of the disease where could be a therapeutic window.