The TRI Thursday Immunology Seminar series will feature exciting research updates from ongoing early-to-mid career Immunology researchers, covering basic to translational research topics in immunology and immunotherapy.

For general enquires regarding the TRI Thursday Immunology Seminar Series, please contact Carmen Taveras and/or Joseph Yunis

Details about the next Immunology Seminar are below.

Date: Thursday 10 August 2023 Time: 9:30am - 10:30am Join: Seminar Room 2003 or Via Zoom

Speaker: Professor Nikolas Haas - Professorial Research Fellow; Head, Experimental Melanoma Therapy Group; Director of Higher Degree Research Frazer Institute; Faculty of Medicine; The University of Queensland; Brisbane, Queensland, Australia Academic Lead of the Translational Research Institute (TRI) Microscopy Core Facility; Brisbane, Queensland, Australia.

Topic:“Overcoming Immune Checkpoint Inhibitor Resistance to Improve Melanoma Therapy". BioNikolas Haass is a clinician scientist and academic leader with research in melanoma cell biology and experimental melanoma therapy. He received his degree in medicine from the University of Heidelberg, Germany (1990-1998). He graduated summa cum laude with a PhD in Cell Biology from the University of Heidelberg (1993-1999) and trained in clinical dermatology at the University of Hamburg, Germany (1999-2003). In 2003 he moved to Philadelphia, PA, USA, for a German Research Foundation (DFG)-sponsored post-doctoral fellowship in Meenhard Herlyn’s lab at The Wistar Institute at University of Pennsylvania (2003-2007). From there he was recruited as an associate faculty member and senior lecturer to the Centenary Institute and to the Department of Dermatology at University of Sydney (2007-2013). In 2013 he commenced his current position as Professor for Cutaneous Oncology at the Frazer Institute at University of Queensland.

Using cutting-edge technology, including real-time cell cycle imaging in 3D culture and in vivo, his team studies the role of dynamic melanoma heterogeneity in melanomagenesis with the goal to develop novel therapeutic approaches by simultaneously targeting different tumor cell subpopulations. His laboratory and team are in the unique position to combine sophisticated imaging and biosensor approaches with biochemical methods to provide unprecedented insight to the mechanisms of tumor heterogeneity, tumor-stroma interactions, and cancer immunology.

His contribution to the field is best evidenced by 98 original papers and invited reviews in leading biomedical journals. Many of his papers have a large impact in the field (>7900 citations in total, and 20 papers cited >100 times each). Some of his papers were evaluated by Faculty 1000 Biology as recommended and exceptional.

AbstractDespite the unprecedented success of immune checkpoint inhibitors (ICI) in cancer therapy, one major unresolved dilemma is treatment resistance. Immunogenic cell death (ICD) constitutes a prominent pathway for the activation of anti-cancer immunity, which in turn determines the long-term success of anticancer therapies. Only a few agents can elicit bona fide ICD, including the proteasome inhibitor bortezomib, as demonstrated in malignant myeloma and mantle cell lymphoma, but not yet in melanoma.

We show that bortezomib causes ICD in vitro through induction of endoplasmic reticulum stress, autophagy and apoptosis and through translocation and/or secretion of damage-associated molecular patterns (DAMPs). Vaccination with bortezomib-treated apoptotic melanoma cells induced tumor immunogenicity in vivo. Intralesional injection of bortezomib synergized with subsequent systemic treatment with ICI. Re-challenge demonstrated long-term protection through bortezomib combined with ICI. Polyfunctional T cell assays revealed that intralesional bortezomib injection generates a tumor-specific T cell response. Importantly, ICI resistance was reverted by bortezomib-induced immunogenicity.

Taken together, bortezomib induces ICD in vitro and immunogenicity in vivo. Bortezomib-induced ICD recruits inflammatory immune response to the tumor site. Bortezomib improves ICI treatment and reverts resistance re-sensitizing mice refractory to ICI.  We propose intralesional injection of bortezomib followed by systemic ICI to improve immune therapy in melanoma.