Single-cell analysis of myeloid cells in HPV+ tonsillar cancer
(2023) In Frontiers in Immunology 13.- Abstract
The incidence of human papillomavirus-positive (HPV+) tonsillar cancer has been sharply rising during the last decades. Myeloid cells represent an appropriate therapeutic target due to their proximity to virus-infected tumor cells, and their ability to orchestrate antigen-specific immunity, within the tonsil. However, the interrelationship of steady-state and inflammatory myeloid cell subsets, and their impact on patient survival remains unexplored. Here, we used single-cell RNA-sequencing to map the myeloid compartment in HPV+ tonsillar cancer. We observed an expansion of the myeloid compartment in HPV+ tonsillar cancer, accompanied by interferon-induced cellular responses both in dendritic cells (DCs)... (More)
The incidence of human papillomavirus-positive (HPV+) tonsillar cancer has been sharply rising during the last decades. Myeloid cells represent an appropriate therapeutic target due to their proximity to virus-infected tumor cells, and their ability to orchestrate antigen-specific immunity, within the tonsil. However, the interrelationship of steady-state and inflammatory myeloid cell subsets, and their impact on patient survival remains unexplored. Here, we used single-cell RNA-sequencing to map the myeloid compartment in HPV+ tonsillar cancer. We observed an expansion of the myeloid compartment in HPV+ tonsillar cancer, accompanied by interferon-induced cellular responses both in dendritic cells (DCs) and monocyte-macrophages. Our analysis unveiled the existence of four DC lineages, two macrophage polarization processes, and their sequential maturation profiles. Within the DC lineages, we described a balance shift in the frequency of progenitor and mature cDC favoring the cDC1 lineage in detriment of cDC2s. Furthermore, we observed that all DC lineages apart from DC5s matured into a common activated DC transcriptional program involving upregulation of interferon-inducible genes. In turn, the monocyte-macrophage lineage was subjected to early monocyte polarization events, which give rise to either interferon-activated or CXCL-producing macrophages, the latter enriched in advanced tumor stages. We validated the existence of most of the single-cell RNA-seq clusters using 26-plex flow cytometry, and described a positive impact of cDC1 and interferon-activated DCs and macrophages on patient survival using gene signature scoring. The current study contributes to the understanding of myeloid ontogeny and dynamics in HPV-driven tonsillar cancer, and highlights myeloid biomarkers that can be used to assess patient prognosis.
(Less)
- author
- Jimenez, David Gomez LU ; Altunbulakli, Can LU ; Swoboda, Sabine LU ; Sobti, Aastha LU ; Askmyr, David LU ; Ali, Ashfaq LU ; Greiff, Lennart LU and Lindstedt, Malin LU
- organization
- publishing date
- 2023-01-19
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- dendritic cell, human papilloma virus, macrophage, myeloid cell, single-cell RNA-sequencing, tonsillar cancer
- in
- Frontiers in Immunology
- volume
- 13
- article number
- 1087843
- publisher
- Frontiers Media S. A.
- external identifiers
-
- scopus:85147267106
- pmid:36741389
- ISSN
- 1664-3224
- DOI
- 10.3389/fimmu.2022.1087843
- language
- English
- LU publication?
- yes
- id
- 55e0f553-93ed-433d-999c-0344ebabf01e
- date added to LUP
- 2023-02-23 14:50:10
- date last changed
- 2024-09-21 08:41:52
@article{55e0f553-93ed-433d-999c-0344ebabf01e, abstract = {{<p>The incidence of human papillomavirus-positive (HPV<sup>+</sup>) tonsillar cancer has been sharply rising during the last decades. Myeloid cells represent an appropriate therapeutic target due to their proximity to virus-infected tumor cells, and their ability to orchestrate antigen-specific immunity, within the tonsil. However, the interrelationship of steady-state and inflammatory myeloid cell subsets, and their impact on patient survival remains unexplored. Here, we used single-cell RNA-sequencing to map the myeloid compartment in HPV<sup>+</sup> tonsillar cancer. We observed an expansion of the myeloid compartment in HPV<sup>+</sup> tonsillar cancer, accompanied by interferon-induced cellular responses both in dendritic cells (DCs) and monocyte-macrophages. Our analysis unveiled the existence of four DC lineages, two macrophage polarization processes, and their sequential maturation profiles. Within the DC lineages, we described a balance shift in the frequency of progenitor and mature cDC favoring the cDC1 lineage in detriment of cDC2s. Furthermore, we observed that all DC lineages apart from DC5s matured into a common activated DC transcriptional program involving upregulation of interferon-inducible genes. In turn, the monocyte-macrophage lineage was subjected to early monocyte polarization events, which give rise to either interferon-activated or CXCL-producing macrophages, the latter enriched in advanced tumor stages. We validated the existence of most of the single-cell RNA-seq clusters using 26-plex flow cytometry, and described a positive impact of cDC1 and interferon-activated DCs and macrophages on patient survival using gene signature scoring. The current study contributes to the understanding of myeloid ontogeny and dynamics in HPV-driven tonsillar cancer, and highlights myeloid biomarkers that can be used to assess patient prognosis.</p>}}, author = {{Jimenez, David Gomez and Altunbulakli, Can and Swoboda, Sabine and Sobti, Aastha and Askmyr, David and Ali, Ashfaq and Greiff, Lennart and Lindstedt, Malin}}, issn = {{1664-3224}}, keywords = {{dendritic cell; human papilloma virus; macrophage; myeloid cell; single-cell RNA-sequencing; tonsillar cancer}}, language = {{eng}}, month = {{01}}, publisher = {{Frontiers Media S. A.}}, series = {{Frontiers in Immunology}}, title = {{Single-cell analysis of myeloid cells in HPV<sup>+</sup> tonsillar cancer}}, url = {{http://dx.doi.org/10.3389/fimmu.2022.1087843}}, doi = {{10.3389/fimmu.2022.1087843}}, volume = {{13}}, year = {{2023}}, }