PhD thesis defense Tamara Verkerk
Exploring the interplay between immune cells and tumors; insights into antigen presentation and tumor immune evasion
On 12 November 2024 (1:00 PM), Sanquin researcher Tamara Verkerk defended her PhD thesis 'Exploring the interplay between immune cells and tumors; insights into antigen presentation and tumor immune evasion' at the University of Amsterdam
Promotor
Prof SM van Ham PhD
Copromotor
RM Spaapen PhD
Venue
Agnietenkapel, University of Amsterdam
Abstract
In this thesis, we generated a panel of HAP1 cells, which are knockout for different proteins of the antigen presentation pathway, that can be used to investigate human leukocyte antigen class I (HLA-I; major histocompatibility complex I, MHC-I) mediated antigen presentation. This panel was used to investigate the presentation of a TAP-independent peptide by TAP-deficient tumors and healthy, TAP-proficient tissues. We found that healthy tissues were also able to present TAP-independent peptides, which underlines the need of thorough validation before clinical targeting of such antigens. Furthermore, we elaborated on proteasome generated spliced-peptides by tumors and their potential for a role in immunotherapy. We concluded that their role will be minimal. We switched to HLA-independent immune activation by first focusing on in vitro expansion of γδ T cells. These and other innate immune cells were assessed for their anti-tumor immune responses towards tumors lacking the protease SPPL3, which results in upregulation of neolacto-series glycosphingolipids (nsGSLs) on tumor cells. Anti-tumor responses by innate immune cells against SPPL3-negative tumor cells was reduced, either through nsGSL-dependent or nsGSL-independent regulation by SPPL3. Altogether, we showed that tumors benefit from nsGSLs in order to escape from anti-tumor responses in vitro and potentially benefit from nsGSL overexpression during tumor growth in vivo.
