Abstract
Tonsillar cancer (TC) and nasopharyngeal cancer (NPC) are associated with high-risk human
papillomavirus (HPV) and Epstein-Barr virus (EBV), respectively. Similarly, benign lesions, known
as laryngeal papilloma (LP), are associated with low-risk HPV. Recent advances have included
immunotherapy as a part of the treatment regimen for recurrent and metastatic HNC and LP,
although with limited response rates.
An in-depth understanding of the genetics of the lesions and molecular underpinnings has
identified molecular changes that may guide patient care. In papers I-III, key immune players,
including CD8+ T cells and antigen-presenting cells (APCs), were studied in NPC and TC. Using
quantitative density of CD8+ T cells in NPC, three phenotypes were defined: "inflamed", "immune-
excluded", and "desert". Based on CD8+ T cells infiltratrion, the inflamed phenotype was
associated with higher survival rates than the "immune-excluded".
In paper II, digital spatial technology was used to further investigate the defined phenotypes.
Higher median expression of protein markers such as CD11c and IDO1 and lower median
expression of fibronectin in NPC stromal regions were associated with improved survival. In paper
III, we demonstrated a correlation between the levels of APCs and CD8+ T cells in HPV+ TC, and
showed that patients with high levels of CD8 transcripts had improved survival
In papers IV-V, we investigated LP using gene expression and flow cytometry and observed an
inverse relationship between CD8+ T cells and neutrophils. In addition, a streptococcus subspecies
was associated with severe clinical symptoms and high neutrophil counts in chronic LP (paper V:
a case report). These findings provide a basis for further investigations of neutrophil and bacterial
associations in HPV-associated lesions.
In conclusion, the cell types and biomarkers investigated in this thesis highlight the immune
heterogeneity of NPC, TC, and LP. Validations in larger patient cohorts are needed to develop
clinically applicable biomarkers for prognostics and patient stratification.
papillomavirus (HPV) and Epstein-Barr virus (EBV), respectively. Similarly, benign lesions, known
as laryngeal papilloma (LP), are associated with low-risk HPV. Recent advances have included
immunotherapy as a part of the treatment regimen for recurrent and metastatic HNC and LP,
although with limited response rates.
An in-depth understanding of the genetics of the lesions and molecular underpinnings has
identified molecular changes that may guide patient care. In papers I-III, key immune players,
including CD8+ T cells and antigen-presenting cells (APCs), were studied in NPC and TC. Using
quantitative density of CD8+ T cells in NPC, three phenotypes were defined: "inflamed", "immune-
excluded", and "desert". Based on CD8+ T cells infiltratrion, the inflamed phenotype was
associated with higher survival rates than the "immune-excluded".
In paper II, digital spatial technology was used to further investigate the defined phenotypes.
Higher median expression of protein markers such as CD11c and IDO1 and lower median
expression of fibronectin in NPC stromal regions were associated with improved survival. In paper
III, we demonstrated a correlation between the levels of APCs and CD8+ T cells in HPV+ TC, and
showed that patients with high levels of CD8 transcripts had improved survival
In papers IV-V, we investigated LP using gene expression and flow cytometry and observed an
inverse relationship between CD8+ T cells and neutrophils. In addition, a streptococcus subspecies
was associated with severe clinical symptoms and high neutrophil counts in chronic LP (paper V:
a case report). These findings provide a basis for further investigations of neutrophil and bacterial
associations in HPV-associated lesions.
In conclusion, the cell types and biomarkers investigated in this thesis highlight the immune
heterogeneity of NPC, TC, and LP. Validations in larger patient cohorts are needed to develop
clinically applicable biomarkers for prognostics and patient stratification.
| Original language | English |
|---|---|
| Qualification | Doctor |
| Awarding Institution |
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| Supervisors/Advisors |
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| Award date | 2023 Apr 21 |
| Place of Publication | Lund |
| Publisher | |
| ISBN (Print) | 978-91-8039-594-6 |
| ISBN (electronic) | 978-91-8039-595-3 |
| Publication status | Published - 2022 Mar 22 |
Bibliographical note
Defence detailsDate: 2023-04-21
Time: 09:00
Place: Lecture Hall Hörsalen, Medicon Village, Scheeletorget 1, Faculty of Engineering LTH, Lund University, Lund. The dissertation will be live streamed, but part of the premises is to be excluded from the live stream.
External reviewer(s)
Name: Dalianis, Tina
Title: Prof. Emeritus
Affiliation: Karolinska Institutet, Sweden.
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Subject classification (UKÄ)
- Other Medical Engineering
- Cancer and Oncology
Free keywords
- Human papilloma virus (HPV)
- Epstein-Barr virus
- tonsillar cancer
- nasopharyngeal cancer
- laryngeal papilloma
- tumour microenvionment
- Immune cells
- flow cytometery
- Spatial proteomics
