The PhD defence will be fully digital and streamed directly using Zoom. The host of the session will moderate the technicalities while the chair of the defence will moderate the disputation.
Ex auditorio questions: the chair of the defence will invite the audience to ask ex auditorio questions either written or oral. This can be requested by clicking 'Participants -> Raise hand'.
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Join the disputation on Zoom
- Request the thesis as pdf (opens e-mail)
Trial lecture 10.15
The role of affinity and specificity of protein interactions in the immune response against cancer
Main research findings
Immunotherapy holds immense promise in treating cancer, yet its effectiveness remains limited in treating most solid tumors due to the presence of immunosuppressive tumor microenvironment (TME), notably M2 macrophages. In her doctoral work, Qindong focused on developing targeting strategies against these cells to enhance cancer immunotherapy.
She discovered prohibitin 1 (PHB1) as a cell surface target recognized by the NW peptide that displayed high affinity for both anti-tumoral M1 and pro-tumoral M2 macrophages. Through screening random peptide phage libraries, several low-affinity phage-displayed peptides that selectively bound to M2 macrophages but not M1 macrophages were selected. By coupling these peptides with a photosensitizer termed IR700, specific elimination of M2 macrophages upon near-infrared light exposure while sparing M1 macrophages was achieved. Surprisingly, even the unmodified M13 phage displayed tropism and exhibited cytotoxicity towards M2 macrophages when combined with IR700 and light irradiation. Additionally, combining IR700 with a phage displaying a cancer-specific peptide killed both cancer cells and M2 macrophages. Furthermore, the investigation into STAT3, pivotal in macrophage polarization, explored PHB chemical ligands with STAT3 inhibition effects, aiming to reprogram M2 macrophages into M1 macrophages. Although STAT3 inhibition did not significantly affect macrophage polarization under their experimental conditions, these findings lay the groundwork for further studies.
Overall, this Ph.D. work advances our understanding of PHBs, demonstrates the utility of phage-displayed peptides in photoimmunotherapy, and investigates the use of PHB ligands in macrophage reprogramming, offering new avenues to reshape the TME for improved cancer immunotherapy.
Read more (in Norwegian)
Kreftsvulsten hjernevaskar kvite blodceller for å få dei til å hjelpa seg (10. mai 2023)