Cell Reports
Volume 40, Issue 7, 16 August 2022, 111171
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Article
During early stages of cancer, neutrophils initiate anti-tumor immune responses in tumor-draining lymph nodes

https://doi.org/10.1016/j.celrep.2022.111171Get rights and content
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Highlights

  • Tumor-associated neutrophils transmigrate to LNs and shape anti-cancer T cell response

  • In non-metastatic stage, LN neutrophils prime T cells and improve patient prognosis

  • Metastatic microenvironment via GM-CSF/STAT3 induces immunosuppressive neutrophils

Summary

Tumor-draining lymph nodes (LNs) play a crucial role during cancer spread and in initiation of anti-cancer adaptive immunity. Neutrophils form a substantial population of cells in LNs with poorly understood functions. Here, we demonstrate that, during head and neck cancer (HNC) progression, tumor-associated neutrophils transmigrate to LNs and shape anti-tumor responses in a stage-dependent manner. In metastasis-free stages (N0), neutrophils develop an antigen-presenting phenotype (HLA-DR+CD80+CD86+ICAM1+PD-L1) and stimulate T cells (CD27+Ki67highPD-1). LN metastases release GM-CSF and via STAT3 trigger development of PD-L1+ immunosuppressive neutrophils, which repress T cell responses. The accumulation of neutrophils in T cell-rich zones of LNs in N0 constitutes a positive predictor for 5-year survival, while increased numbers of neutrophils in LNs of N13 stages predict poor prognosis in HNC. These results suggest a dual role of neutrophils as essential regulators of anti-cancer immunity in LNs and argue for approaches fostering immunostimulatory activity of these cells during cancer therapy.

Research topic(s)

CP: Cancer
CP: Immunology

Keywords

neutrophils
antigen-presenting cells
lymph nodes
adaptive immunity
T lymphocytes
immunosuppression
head and neck cancer
cancer
tumor
metastasis

Data and code availability

  • Data: This paper analyzes existing, publicly available data from Gene Expression Omnibus databases. These accession numbers for the datasets are listed in the key resources table.

  • Code: All original code is available in this paper’s supplemental information (List S1).

  • Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

Cited by (0)

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Lead contact