Doctoral themes 2023

Development of a microcalorimetry-based biomarker for T cell immunotherapy

Supervisors

 Fernando Antunes, fantunes@ciencias.ulisboa.pt

Carlos Bernardes, cebernardes@ciencias.ulisboa.pt

Registration Institution

Faculdade de Ciências, Universidade de Lisboa

Project description

 The long-term objective of this project is to identify biomarkers for cellular therapies, such as adoptive immunotherapy. Toward this objective, we aim to detect early adaptive cellular responses to alterations of the conditions in which cells operate before cellular function is compromised. This detection is based on the energy dissipated by cells in the form of heat, which is measured by calorimetry. Heat constitutes a global parameter of the state of a living cell that measures the effort cells are using to perform their functions. This new idea resulted from the cross-fertilization of team expertise in biochemistry and thermodynamics and will be implemented in groups 5 and 9, having Swedish company Symcell as a partner. In addition, a stay at Department of Immunology IBISS, University of Belgrade, Serbia under supervision of Đorđe Miljković is planned.

Here, this innovative idea is applied to detect T-cell exhaustion. Upon an immunological stimulus quiescent T-cells are activated for proliferation and exert their immunological functions. T-cell exhaustion in broad terms describes their dysfunctional response to immunological stimuli. We will test whether heat measurements detect T-cell exhaustion before any of the commonly employed parameters detects this phenomenon as T-cell dysfunctionality starts to evolve. Validation of this hypothesis has high clinical impact, because it could be applied to: (1) predict a poor response of patients to T-cell immunotherapy for cancer; (2) anticipate the onset of cancer resistance during T-cell immunotherapy, allowing to switch therapies before metastasis occurs; and, (3) predict the efficacy of vaccines in elderly individuals.

Keywords

Biomarkers

Calorimetry

Energy dissipation

T-cell exhaustion

Immunotherapy