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998 Neutrophil subsets in head and neck cancer
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  1. Sandra Ekstedt1,
  2. Krzysztof Piersiala1,
  3. Magnus Starkhammar2,
  4. Gregori Margolin2,
  5. Susanna Kumlien Georén1 and
  6. Lars Olaf Cardell1
  1. 1Karolinska Institutet, Solletnuna, Sweden
  2. 2Karolinska University Hospital, Solna, Sweden

Abstract

Background The neutrophil is the first cell recruited to the site of inflammation in HNSCC.1 Neutrophils have been perceived as a relatively homogenous cell type. However, our group has demonstrated that neutrophils can be divided into different subsets.2-5 and we have identified a subset that can migrate into the tumour in HNSCC patients.6 HNSCC may promote a shift towards more activated neutrophil subsets and the neutrophils may thereafter migrate to the lymph nodes.

Methods Thanks to our unique access to unfixed samples of lymph nodes and tumour biopsies of patients with oral HNSCC were we able to identify neutrophil subsets in each tissue and compare them to neutrophils found in the blood. The tissue, homogenized to a single cell suspension, and blood were analyzed with flow cytometry.

Results There are more CD16HighCD62LHigh Neutrophils in the blood compared to lymph nodes and the tumour tissue. The neutrophils subset CD16HighCD62Ldim neutrophils are found mainly in the lymph node of the cancer patients and the subset CD16dimCD62dim is almost only present in the tumour site. In healthy lymph nodes is the dominant subset CD16HighCD62LHigh.

Conclusions Our study suggests that neutrophil subsets have different functions and play role in HNSCC.

References

  1. Decker AS, Pylaeva E, Brenzel A, Spyra I, Droege F, Hussain T, et al. Prognostic Role of Blood NETosis in the Progression of Head and Neck Cancer. Cells 2019;8(9).

  2. Pillay J, Kamp VM, van Hoffen E, Visser T, Tak T, Lammers JW, et al. A subset of neutrophils in human systemic inflammation inhibits T cell responses through Mac-1. The Journal of Clinical Investigation 2012;122(1):327–36.

  3. Ekstedt S, Stenberg H, Tufvesson E, Diamant Z, Bjermer L, Kumlien Georen S, et al. The potential role of CD16(high) CD62L(dim) neutrophils in the allergic asthma. Allergy 2019;74(11):2265–8.

  4. Ekstedt S, Tufvesson E, Bjermer L, Kumlien Georen S, Cardell LO. A new role for "eat me" and "don't eat me" markers on neutrophils in asthmatic airway inflammation. Allergy. 2020.

  5. Ekstedt S, Safholm J, Georen SK, Cardell LO. Dividing neutrophils in subsets reveals a significant role for activated neutrophils in the development of airway hyperreactivity. Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology. 2019;49(3):285–91.

  6. Millrud CR, Kagedal A, Kumlien Georen S, Winqvist O, Uddman R, Razavi R, et al. NET-producing CD16(high) CD62L(dim) neutrophils migrate to tumor sites and predict improved survival in patients with HNSCC. International Journal of Cancer. 2017;140(11):2557–67.

Ethics Approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the Swedish national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study. Ethics Committee Approvals: 2015/1650-31/2 and 2019-03518.

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