Dataset Information

Region-Specific CD16⁺ Neutrophils Promote Colorectal Cancer Progression by Inhibiting Natural Killer Cells.

ABSTRACT: The colon is the largest compartment of the immune system, with innate immune cells exposed to antigens in the environment. However, the mechanisms by which the innate immune system is instigated are poorly defined in colorectal cancer (CRC). Here, a population of CD16⁺ neutrophils that specifically accumulate in CRC tumor tissues by imaging mass cytometry (IMC), immune fluorescence, and flow cytometry, which demonstrated pro-tumor activity by disturbing natural killer (NK) cells are identified. It is found that these CD16⁺ neutrophils possess abnormal cholesterol accumulation due to activation of the CD16/TAK1/NF-κB axis, which upregulates scavenger receptors for cholesterol intake including CD36 and LRP1. Consequently, these region-specific CD16⁺ neutrophils not only competitively inhibit cholesterol intake of NK cells, which interrupts NK lipid raft formation and blocks their antitumor signaling but also release neutrophil extracellular traps (NETs) to induce the death of NK cells. Furthermore, CD16-knockout reverses the pro-tumor activity of neutrophils and restored NK cell cytotoxicity. Collectively, the findings suggest that CRC region-specific CD16⁺ neutrophils can be a diagnostic marker and potential therapeutic target for CRC.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC11304263 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Publications

Region-Specific CD16<sup>+</sup> Neutrophils Promote Colorectal Cancer Progression by Inhibiting Natural Killer Cells.

Zhang Yan Y Wang Zien Z Lu Yu Y Sanchez David J DJ Li Jiaojiao J Wang Linghao L Meng Xiaoxue X Chen Jianjun J Kien Tran Trung TT Zhong Ming M Gao Wei-Qiang WQ Ding Xianting X

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20240524 29

The colon is the largest compartment of the immune system, with innate immune cells exposed to antigens in the environment. However, the mechanisms by which the innate immune system is instigated are poorly defined in colorectal cancer (CRC). Here, a population of CD16<sup>+</sup> neutrophils that specifically accumulate in CRC tumor tissues by imaging mass cytometry (IMC), immune fluorescence, and flow cytometry, which demonstrated pro-tumor activity by disturbing natural killer (NK) cells are ...[more]

PMID: 38790136

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Project description:Natural killer (NK) cells are innate cytotoxic and immunoregulatory lymphocytes that have a central role in anti-tumor immunity and play a critical role in mediating cellular immunity in advanced cancer immunotherapies, such as dendritic cell (DC) vaccines. Our group recently tested a novel recombinant adenovirus-transduced autologous DC-based vaccine that simultaneously induces T cell responses against three melanoma-associated antigens for advanced melanoma patients. Here, we examine the impact of this vaccine as well as the subsequent systemic delivery of high-dose interferon-α2b (HDI) on the circulatory NK cell profile in melanoma patients. At baseline, patient NK cells, particularly those isolated from high-risk patients with no measurable disease, showed altered distribution of CD56dim CD16+ and CD56dim CD16- NK cell subsets, as well as elevated serum levels of immune suppressive MICA, TN5E/CD73 and tactile/CD96, and perforin. Surprisingly, patient NK cells displayed a higher level of activation than those from healthy donors as measured by elevated CD69, NKp44 and CCR7 levels, and enhanced K562 killing. Elevated cytolytic ability strongly correlated with increased representation of CD56dim CD16+ NK cells and amplified CD69 expression on CD56dim CD16+ NK cells. While intradermal DC immunizations did not significantly impact circulatory NK cell activation and distribution profiles, subsequent HDI injections enhanced CD56bright CD16- NK cell numbers when compared to patients that did not receive HDI. Phenotypic analysis of tumor-infiltrating NK cells showed that CD56dim CD16- NK cells are the dominant subset in melanoma tumors. NanoString transcriptomic analysis of melanomas resected at baseline indicated that there was a trend of increased CD56dim NK cell gene signature expression in patients with better clinical response. These data indicate that melanoma patient blood NK cells display elevated activation levels, that intra-dermal DC immunizations did not effectively promote systemic NK cell responses, that systemic HDI administration can modulate NK cell subset distributions and suggest that CD56dim CD16- NK cells are a unique non-cytolytic subset in melanoma patients that may associate with better patient outcome.

Dataset Information

Region-Specific CD16⁺ Neutrophils Promote Colorectal Cancer Progression by Inhibiting Natural Killer Cells.

Publications

Region-Specific CD16<sup>+</sup> Neutrophils Promote Colorectal Cancer Progression by Inhibiting Natural Killer Cells.

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OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

Region-Specific CD16+ Neutrophils Promote Colorectal Cancer Progression by Inhibiting Natural Killer Cells.

Publications

Region-Specific CD16<sup>+</sup> Neutrophils Promote Colorectal Cancer Progression by Inhibiting Natural Killer Cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Region-Specific CD16⁺ Neutrophils Promote Colorectal Cancer Progression by Inhibiting Natural Killer Cells.