Single-cell proteomics maps circulating monocyte dynamics in advanced head and neck squamous cell carcinoma

Abstract

It remains unclear whether metastatic progression in head and neck squamous cell carcinoma (HNSCC) is accompanied by functional remodeling of circulating immune cells at the proteome level. To address this question, we applied single-cell proteomics (SCP) to cryopreserved peripheral blood mononuclear cells (PBMCs) from three patients with HNSCC representing distinct stages of metastatic progression and two healthy donors. Proteomic analysis of 619 individual PBMCs resolved major immune cell populations, with up to 1,638 proteins quantified per cell. Trajectory inference, clustering, and differential abundance analyses revealed proteomic remodeling associated with disease progression, with the most pronounced changes occurring within a monocyte cluster composed exclusively of cells from patients with nodal metastasis. This population showed increased abundance of interferon-related proteins, HLA molecules, and myeloid immunoregulatory signatures, consistent with an activated, interferon-associated monocyte state. In parallel, lymphocytes showed reduced coordinated abundance of proteins associated with activation, cytotoxicity, and degranulation, consistent with altered cytotoxic effector programs across disease stages. Overall, these findings reveal distinct proteomic states in circulating monocytes and lymphocytes associated with HNSCC progression and identify selective remodeling of the monocyte compartment in nodal metastatic disease.

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BibTeX RIS

BibTeX

@misc{prado2026singlecell,
  title = {{Single-cell proteomics maps circulating monocyte dynamics in advanced head and neck squamous cell carcinoma}},
  author = {H. M. d. A. Prado and J. G. Miyamoto and A. F. Busso-Lopes and N. A. d. R. Coimbra and D. de Figueiredo and R. R. Domingues and B. A. Pauletti and A. L. Mores and T. d. S. Medina and R. N. Ramos and T. B. Brandao and A. C. Prado-Ribeiro and L. P. Kowalski and A. Paes Leme},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.08.750082},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.08.750082v1},
  note = {CC BY-NC-ND},
}

RIS

TY  - UNPB
TI  - Single-cell proteomics maps circulating monocyte dynamics in advanced head and neck squamous cell carcinoma
AU  - H. M. d. A. Prado
AU  - J. G. Miyamoto
AU  - A. F. Busso-Lopes
AU  - N. A. d. R. Coimbra
AU  - D. de Figueiredo
AU  - R. R. Domingues
AU  - B. A. Pauletti
AU  - A. L. Mores
AU  - T. d. S. Medina
AU  - R. N. Ramos
AU  - T. B. Brandao
AU  - A. C. Prado-Ribeiro
AU  - L. P. Kowalski
AU  - A. Paes Leme
PY  - 2026
DA  - 2026/09/08
PB  - bioRxiv
DO  - 10.64898/2026.09.08.750082
UR  - https://www.biorxiv.org/content/10.64898/2026.09.08.750082v1
AB  - It remains unclear whether metastatic progression in head and neck squamous cell carcinoma (HNSCC) is accompanied by functional remodeling of circulating immune cells at the proteome level. To address this question, we applied single-cell proteomics (SCP) to cryopreserved peripheral blood mononuclear cells (PBMCs) from three patients with HNSCC representing distinct stages of metastatic progression and two healthy donors. Proteomic analysis of 619 individual PBMCs resolved major immune cell populations, with up to 1,638 proteins quantified per cell. Trajectory inference, clustering, and differential abundance analyses revealed proteomic remodeling associated with disease progression, with the most pronounced changes occurring within a monocyte cluster composed exclusively of cells from patients with nodal metastasis. This population showed increased abundance of interferon-related proteins, HLA molecules, and myeloid immunoregulatory signatures, consistent with an activated, interferon-associated monocyte state. In parallel, lymphocytes showed reduced coordinated abundance of proteins associated with activation, cytotoxicity, and degranulation, consistent with altered cytotoxic effector programs across disease stages. Overall, these findings reveal distinct proteomic states in circulating monocytes and lymphocytes associated with HNSCC progression and identify selective remodeling of the monocyte compartment in nodal metastatic disease.
ER  -

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