Aaron Rosado

BME PhD Proposal Presenation

Date: December 3rd, 2018

Time: 1:00pm

Location: McIntire Room

Advisor: Cheng Zhu

Committee Members: 

Arash Grakoui (Emory)

Susan Thomas (BME)

Michael Davis (BME)

Michelle Krogsgaard (NYU)

Title: Impairment of Mechanosensing and Lateral Crosstalk Among Immune Receptors in Tumor Infiltrating Lymphocytes

Abstract/Summary:

The tumor microenvironment’s (TME) unique immune characteristics play a major role in shaping tumor immune responses.  Immune cells infiltrating into the tumor microenvironment encounter unique microenvironmental cues potentially resulting in anti-tumor immune response suppression.  Immune checkpoint blockade (ICB) attempts to suppress inhibitory immune checkpoint receptors in ways that enhance anti-tumor immunity.  Although ICB clearly enhances cytotoxic potential in infiltrating cytotoxic T cells, many questions remain about immune checkpoint receptors function within the TME.  We propose that the TME impairs infiltrating cytotoxic T cell CD8, CD28, CTLA-4, and TCR complex mechanosensing and lateral crosstalk (LC).  We will investigate TME immune synapse receptor mechanosensing and LC impairment in infiltrating cytotoxic T cells with bond quality and quantity measurements.  We will employ biomechanical switching instrument techniques towards controlling LC spatially and temporally.  We will demonstrate immune synapse receptor mechanosensing and LC impairment functionally impairs T cell function and can be modulated with small molecule inhibitors.  We believe investigations into mechanosensing and LC impairment will provide invaluable immune checkpoint signaling insights and motivate cancer immunotherapy improvements.