Single-cell analysis of myeloid cells in HPV+ tonsillar cancer

被引:3
作者
Jimenez, David Gomez [1 ]
Altunbulakli, Can [1 ]
Swoboda, Sabine [2 ,3 ]
Sobti, Aastha [1 ]
Askmyr, David [2 ,3 ]
Ali, Ashfaq [1 ,4 ]
Greiff, Lennart [2 ,3 ]
Lindstedt, Malin [1 ]
机构
[1] Lund Univ, Dept Immunotechnol, Lund, Sweden
[2] Skane Univ Hosp, Dept ORL Head & Neck Surg, Lund, Sweden
[3] Lund Univ, Dept Clin Sci, Lund, Sweden
[4] Lund Univ, Sci Life Lab, Natl Bioinformat Infrastructure Sweden, Lund, Sweden
来源
FRONTIERS IN IMMUNOLOGY | 2023年 / 13卷
关键词
tonsillar cancer; human papilloma virus; myeloid cell; dendritic cell; single-cell RNA-sequencing; macrophage; DENDRITIC CELLS; HUMAN-PAPILLOMAVIRUS; SUPPRESSOR-CELLS; MACROPHAGES; HEAD; DIFFERENTIATION; CARCINOMA; MATURATION; CAPACITY; ANTIGEN;
D O I
10.3389/fimmu.2022.1087843
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
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页数:18
相关论文
共 104 条
[1]  
Aibar S, 2017, NAT METHODS, V14, P1083, DOI [10.1038/nmeth.4463, 10.1038/NMETH.4463]
[2]   Defining the emergence of myeloid-derived suppressor cells in breast cancer using single-cell transcriptomics [J].
Alshetaiwi, Hamad ;
Pervolarakis, Nicholas ;
McIntyre, Laura Lynn ;
Ma, Dennis ;
Quy Nguyen ;
Rath, Jan Akara ;
Nee, Kevin ;
Hernandez, Grace ;
Evans, Katrina ;
Torosian, Leona ;
Silva, Anushka ;
Walsh, Craig ;
Kessenbrock, Kai .
SCIENCE IMMUNOLOGY, 2020, 5 (44)
[3]   destiny: diffusion maps for large-scale single cell data in R [J].
Angerer, Philipp ;
Haghverdi, Laleh ;
Buettner, Maren ;
Theis, Fabian J. ;
Marr, Carsten ;
Buettner, Florian .
BIOINFORMATICS, 2016, 32 (08) :1241-1243
[4]   Gene Ontology: tool for the unification of biology [J].
Ashburner, M ;
Ball, CA ;
Blake, JA ;
Botstein, D ;
Butler, H ;
Cherry, JM ;
Davis, AP ;
Dolinski, K ;
Dwight, SS ;
Eppig, JT ;
Harris, MA ;
Hill, DP ;
Issel-Tarver, L ;
Kasarskis, A ;
Lewis, S ;
Matese, JC ;
Richardson, JE ;
Ringwald, M ;
Rubin, GM ;
Sherlock, G .
NATURE GENETICS, 2000, 25 (01) :25-29
[5]   The Generation and Identity of Human Myeloid-Derived Suppressor Cells [J].
Bergenfelz, Caroline ;
Leandersson, Karin .
FRONTIERS IN ONCOLOGY, 2020, 10
[6]   Unleashing Type-2 Dendritic Cells to Drive Protective Antitumor CD4+ T Cell Immunity [J].
Binnewies, Mikhail ;
Mujal, Adriana M. ;
Pollack, Joshua L. ;
Combes, Alexis J. ;
Hardison, Emily A. ;
Barry, Kevin C. ;
Tsui, Jessica ;
Ruhland, Megan K. ;
Kersten, Kelly ;
Abushawish, Marwan A. ;
Spasic, Marko ;
Giurintano, Jonathan P. ;
Chan, Vincent ;
Daud, Adil, I ;
Ha, Patrick ;
Ye, Chun J. ;
Roberts, Edward W. ;
Krummel, Matthew F. .
CELL, 2019, 177 (03) :556-+
[7]   NK Cells Stimulate Recruitment of cDC1 into the Tumor Microenvironment Promoting Cancer Immune Control [J].
Boettcher, Jan P. ;
Bonavita, Eduardo ;
Chakravarty, Probir ;
Blees, Hanna ;
Cabeza-Cabrerizo, Mar ;
Sammicheli, Stefano ;
Rogers, Neil C. ;
Sahai, Erik ;
Zelenay, Santiago ;
Reis e Sousa, Caetano .
CELL, 2018, 172 (05) :1022-+
[8]   Transcriptional and Functional Analysis of CD1c+ Human Dendritic Cells Identifies a CD163+ Subset Priming CD8+CD103+ T Cells [J].
Bourdely, Pierre ;
Anselmi, Giorgio ;
Vaivode, Kristine ;
Ramos, Rodrigo Nalio ;
Missolo-Koussou, Yoann ;
Hidalgo, Sofia ;
Tosselo, Jimena ;
Nunez, Nicolas ;
Richer, Wilfrid ;
Vincent-Salomon, Anne ;
Saxena, Alka ;
Wood, Kristie ;
Lladser, Alvaro ;
Piaggio, Eliane ;
Helft, Julie ;
Guermonprez, Pierre .
IMMUNITY, 2020, 53 (02) :335-+
[9]   Human dendritic cells (DCs) are derived from distinct circulating precursors that are precommitted to become CD1c+ or CD141+ DCs [J].
Breton, Gaelle ;
Zheng, Shiwei ;
Valieris, Renan ;
da Silva, Israel Tojal ;
Satija, Rahul ;
Nussenzweig, Michel C. .
JOURNAL OF EXPERIMENTAL MEDICINE, 2016, 213 (13) :2861-2870
[10]   Transcriptional Basis of Mouse and Human Dendritic Cell Heterogeneity [J].
Brown, Chrysothemis C. ;
Gudjonson, Herman ;
Pritykin, Yuri ;
Deep, Deeksha ;
Lavallee, Vincent-Philippe ;
Mendoza, Alejandra ;
Fromme, Rachel ;
Mazutis, Linas ;
Ariyan, Charlotte ;
Leslie, Christina ;
Pe'er, Dana ;
Rudensky, Alexander Y. .
CELL, 2019, 179 (04) :846-+