Treatment-induced antigen presentation in cancer
- Determination of self versus non-self is vital to the health of all organisms, and is in part determined by Major Histocompatibility Complex (MHC) proteins in mammals. While evolved to protect against pathogens, MHC molecules may also present tumor-associated antigens to cell surfaces for T-cell surveillance. Presentation of tumor-associated antigens on MHC is vital for efficacy of most currently available immunotherapy regimens. Therefore, cancer immunotherapy treatments such as Immune Checkpoint Blockade are ineffective in malignancies that have mid- to low- Tumor Mutation Burden (TMB). This work outlines the effect of three treatments on various human cancer cell lines. The first study determines the effect of mTOR inhibitor rapamycin on Burkitt Lymphoma (Raji) cells and concludes that rapamycin upregulates the expression of several MHC molecules, leading to the presentation of more unique peptides. The second study analyzes the effect of interferon-gamma, a cytokine that upregulates the expression of MHC molecules as well as other components of the antigen processing and presentation (APP) pathway. Our results indicate that interferon-gamma increases the proteome coverage of MHC-associated peptides due to these effects on APP proteins. The final study in this work elucidates the effect of gamma-irradiation on the head and neck squamous cell carcinoma (HNSCC) cell line, PCI-13, in a 3D cell-derived xenograft model. The results of gamma-irradiation were surprising: irradiated tumors had markedly fewer MHC-associated peptides than matched controls. In conclusion, exogenous perturbations can have dramatic effects on antigen presentation and should be studied further in order to better understand how cancer therapeutics affect antigen presentation, and therefore immunotherapy efficacy.
|Type of resource
|electronic resource; remote; computer; online resource
|1 online resource.
|Heberling, Marlene Louise
|Degree committee member
|Stanford University, Department of Chemical and Systems Biology
|Statement of responsibility
|Marlene L. Heberling.
|Submitted to the Department of Chemical and Systems Biology.
|Thesis Ph.D. Stanford University 2022.
- © 2022 by Marlene Louise Heberling
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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