Dr. Dr. Bertram Bengsch
T cells are key to the ability of the immune system to control infection, cancer and prevention of autoimmunity. However, in chronic disease, such as chronic Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) infection, hepatocellular carcinoma (HCC), or inflammatory bowel disease (IBD), T cell functionality is altered and inefficient in preventing pathology.
We are interested in how the T cell response is regulated during chronic disease and how immunotherapeutic interventions can augment function.
A major focus in the lab is centered on understanding exhausted T cells (TEX), which constitute a T cell lineage distinct from functional memory and effector cells that is characterized by co-expression of immunoregulatory molecules, an altered transcriptional and epigenetic landscape and reduced effector and memory functionality. We have recently demonstrated that bioenergetic regulation through immune checkpoints (e.g., PD-1) is an important driver of exhaustion. Further, we have demonstrated heterogeneity and disease associations of different varieties of exhausted T cells in humans that are impacted by therapy.
Our translational research is currently focused on chronic HBV and HCV infection and HCC. We interrogate TEX prior to and during antiviral or checkpoint therapies (e.g., anti-PD-1, anti-CTLA-4) using both targeted and systems immunology approaches. We further aim to dissect the impact of metabolic regulation through integration of signaling via immunoregulatory receptors and environmental factors on T cell exhaustion. Understanding the regulation of exhausted T cells has major implications for immunotherapeutic approaches in infection, cancer and autoimmunity.
10 selected publications
- Bioenergetic insufficiencies due to metabolic alterations are an early driver of CD8 T cell exhaustion.
Bengsch B, Johnson AL, Kurachi M, Odorizzi PM, Pauken KE, Attanasio J, Stelekati E, McLane LM, Paley MA, Delgoffe GM, Wherry EJ.
- T-cell invigoration to tumour burden ratio associated with anti-PD-1 response.
Huang AC, Postow MA, Orlowski RJ, Mick R, Bengsch B, Manne S, Xu W, Harmon S, Giles JR, Wenz B, Adamow M, Kuk D, Panageas K, Carrera C, Wong P, Quagliarello F, Wubbenhorst B, D’Andrea K, Gimotty PA, Buckley M, Pauken KE, Herati RS, Staupe RP, Schenkel JM, McGettigan S, Kothari S, George SM, Amaravadi RK, Karakousis GC, Schuchter LM, Xu X, Nathanson KL, Wolchok JD, Gangadhar TC, Wherry EJ.
- Deep immune profiling by mass cytometry links human T and NK cell differentiation and cytotoxic molecule expression patterns.
Bengsch B, Ohtani T, Herati RS, Bovenschen N, Chang KM, Wherry EJ.
J Immunol Methods. 2017; pii: S0022-1759(17)30132-1.
- Epigenetic stability of exhausted T cells limits durability of reinvigoration by PD-1 blockade.
Pauken KE, Sammons MA, Odorizzi PM, Manne SK, Godec J, Khan O, Drake AM, Chen Z, Sen D, Kurachi M, Barnitz RA, Bartman C, Bengsch B, Huang AC, Schenkel JM, Vahedi G, Haining WN, Berger SL, Wherry EJ.
- Comprehensive intestinal T Helper Cell profiling reveals specific accumulation of IFN-γ+IL-17+coproducing CD4+ T cells in active inflammatory bowel disease.
Globig AM, Hennecke N, Martin B, Seidl M, Ruf G, Hasselblatt P, Thimme R, Bengsch B.
Inflamm Bowel Dis. 2014;20(12):2321-9.
- Restoration of HBV-specific CD8+ T-cell function by PD-1 blockade in inactive carrier patients is linked to T-cell differentiation.
Bengsch B, Martin B, Thimme R.
J Hepatol. 2014;61(6):1212-9
- Coexpression of PD-1, 2B4, CD160 and KLRG1 on exhausted HCV-specific CD8+ T cells is linked to antigen recognition and T cell differentiation.
Bengsch B*, Seigel B*, Ruhl M, Timm J, Kuntz M, Blum HE, Pircher H, Thimme R.
PLoS Pathog 2010;6:e1000947.
- Human Th17 Cells Express High Levels of Enzymatically Active Dipeptidylpeptidase IV (CD26).
Bengsch B*, Seigel B*, Flecken T, Wolanski J, Blum HE, Thimme R.
J Immunol 2012;188:5438-47.
- Factors that determine the antiviral efficacy of HCV-specific CD8(+) T cells ex vivo.
Seigel B, Bengsch B, Lohmann V, Bartenschlager R, Blum HE, Thimme R.
- Low perforin expression of early differentiated HCV-specific CD8+ T cells limits their hepatotoxic potential.
Bengsch B*, Jo J*, Seigel B*, Rau SJ*, Schmidt J, Bisse E, Aichele P, Aichele U, Joeckel L, Royer C, Ferreira KS, Borner C, Baumert TF, Blum HE, Lohmann V, Fischer R, Thimme R.
J Hepatol 2012;57(1):9-16