Scholarlink

Background <p>Neutrophils are the most abundant granulocytes in the tumor microenvironment and exert both pro- and anti-cancer effects. Activated neutrophils can release neutrophil extracellular traps (NETs) that have been proposed to promote tumor progression and metastasis. We aimed to clarify the significance of NETs and granulocytes in colorectal cancer.</p> Methods <p>Our study population consisted of three independent colorectal cancer cohorts (<i>N</i> = 1927). We identified NETs showing positivity for citrullinated histone H3 (Cit-H3) and granulocytes expressing CD66b (CEACAM8) with multiplex immunohistochemistry and used digital image analysis and machine learning tools to calculate their densities in tumor samples. Associations between NET and granulocyte densities with clinicopathologic characteristics, tumor-infiltrating immune cells, prognosis, and systemic inflammation markers were examined.</p> Results <p>The densities of Cit-H3<sup>+</sup> NETs positively correlated with macrophage densities and mesenteric serum levels of CX3CL1 and ANGPT2, but were not associated with survival. Higher CD66b<sup>+</sup> granulocyte density was associated with longer colorectal cancer-specific survival independent of conventional prognostic parameters. In the largest cohort (<i>N</i> = 1090), multivariable HR for high vs. low CD66b<sup>+</sup> granulocyte density was 0.53 (95%CI 0.38–0.73, <i>P</i><sub>Trend</sub> &lt; 0.001).</p> Conclusion <p>Our findings indicate that while neutrophil infiltration is associated with favorable colorectal cancer outcomes, the presence of intratumoral Cit-H3<sup>+</sup> NETs does not predict survival.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Significance of tumor infiltrating granulocytes and neutrophil extracellular traps in colorectal cancer

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月7日

查看全文
  • Oskari Rahkola,
  • Anne Tuomisto,
  • Hanna Elomaa,
  • Henna Karjalainen,
  • Ville K. Äijälä,
  • Meeri Kastinen,
  • Vilja V. Tapiainen,
  • Akseli Kehusmaa,
  • Aino Ojanperä,
  • Vesa-Matti Pohjanen,
  • Maarit Ahtiainen,
  • Olli Helminen,
  • Erkki-Ville Wirta,
  • Jukka Rintala,
  • Sanna Meriläinen,
  • Raila Aro,
  • Reetta Häivälä,
  • Juha Saarnio,
  • Tero Rautio,
  • Toni T. Seppälä,
  • Jan Böhm,
  • Jukka-Pekka Mecklin,
  • Markus J. Mäkinen,
  • Juha P. Väyrynen,
  • Päivi Sirniö

摘要

Background

Neutrophils are the most abundant granulocytes in the tumor microenvironment and exert both pro- and anti-cancer effects. Activated neutrophils can release neutrophil extracellular traps (NETs) that have been proposed to promote tumor progression and metastasis. We aimed to clarify the significance of NETs and granulocytes in colorectal cancer.

Methods

Our study population consisted of three independent colorectal cancer cohorts (N = 1927). We identified NETs showing positivity for citrullinated histone H3 (Cit-H3) and granulocytes expressing CD66b (CEACAM8) with multiplex immunohistochemistry and used digital image analysis and machine learning tools to calculate their densities in tumor samples. Associations between NET and granulocyte densities with clinicopathologic characteristics, tumor-infiltrating immune cells, prognosis, and systemic inflammation markers were examined.

Results

The densities of Cit-H3+ NETs positively correlated with macrophage densities and mesenteric serum levels of CX3CL1 and ANGPT2, but were not associated with survival. Higher CD66b+ granulocyte density was associated with longer colorectal cancer-specific survival independent of conventional prognostic parameters. In the largest cohort (N = 1090), multivariable HR for high vs. low CD66b+ granulocyte density was 0.53 (95%CI 0.38–0.73, PTrend < 0.001).

Conclusion

Our findings indicate that while neutrophil infiltration is associated with favorable colorectal cancer outcomes, the presence of intratumoral Cit-H3+ NETs does not predict survival.