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Objective: High density of tumor-infiltrating lymphocytes (TIL) in the tumor is associated with favorable prognosis of cancer patients. It has been reported that many neutrophils also infiltrate in various tumor tissues as tumor-associated neutrophils (TAN) which produce considerable amounts of neutrophil extracellular traps (NETs). However, the crosstalk between TAN and TIL and its impact on tumor behavior have not been fully examined. Methods: Neutrophils and mononuclear cells (PBMC) were collected from the blood of healthy donor. Neutrophils were stimulated with PMA or LPS for 15 min, washed extensively, and incubated for another 4 hours to produce NETs. PBMC were cultured on anti-CD3 mAb-coated plate with recombinant-IL-2 for 7-14days. The migration of activated T cells through 3μm pore to CXCL-11 was examined in vitro. The localization and densities of TAN and TIL were immunohistochemically evaluated in 38 human serous ovarian cancer tissue. NETs were quantified with the density of CD66b(+) and Citrullinated Histon H3(+) cells. Results: Chemotactic migration of T cells to CXCL-11 was inhibited by 99%±1.6% (p Conclusion: Activated neutrophils negatively regulate T cell migration partially through NET formation. TAN may suppress T cell traffic into tumor tissue, which may attenuate cell-mediated immunity in tumor microenvironment and promote tumor progression. Citation Format: Kohei Tamura, Hideyo Miyato, Misaki Matsumiya, Rei Takahashi, Yuki Kaneko, Yurie Futoh, Kazuya Takahashi, Yuki Kimura, Akira Saito, Hideyuki Ohzawa, Yasushi Saga, Yuji Takei, Hiroyuki Fujiwara, Joji Kitayama. Tumor associated neutrophils (TAN) may produce neutrophil extracellular traps (NETs) which can suppress the infiltration of activated T cells in tumor tissue [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2266. |
