Role of Tumor-Associated Neutrophils in the Molecular Carcinogenesis of the Lung

Taucher, Elisabeth; Taucher, Valentin; Fink-Neuboeck, Nicole; Lindenmann, Joerg; Smolle‐Jüttner, Freyja‐Maria

doi:10.3390/cancers13235972

Cited by 12 publications

(7 citation statements)

References 108 publications

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“…However, only more recently has the important role of neutrophils in cancer has been recognized [ 35 ]. The exact functional contributions of neutrophils in cancer appear complex and are not completely understood, as they have been described to stimulate tumor growth, but may also have prominent anti-tumor effects, depending on circumstances [ 35 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ]. Neutrophils in the TME are also referred to as tumor-associated neutrophils (TANs).…”

Section: Neutrophils and Their Role In Cancermentioning

confidence: 99%

Targeting the CD47-SIRPα Innate Immune Checkpoint to Potentiate Antibody Therapy in Cancer by Neutrophils

Behrens

Berg

Egmond

2022

Cancers

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In the past 25 years, a considerable number of therapeutic monoclonal antibodies (mAb) against a variety of tumor-associated antigens (TAA) have become available for the targeted treatment of hematologic and solid cancers. Such antibodies opsonize cancer cells and can trigger cytotoxic responses mediated by Fc-receptor expressing immune cells in the tumor microenvironment (TME). Although frequently ignored, neutrophils, which are abundantly present in the circulation and many cancers, have demonstrated to constitute bona fide effector cells for antibody-mediated tumor elimination in vivo. It has now also been established that neutrophils exert a unique mechanism of cytotoxicity towards antibody-opsonized tumor cells, known as trogoptosis, which involves Fc-receptor (FcR)-mediated trogocytosis of cancer cell plasma membrane leading to a lytic/necrotic type of cell death. However, neutrophils prominently express the myeloid inhibitory receptor SIRPα, which upon interaction with the ‘don’t eat me’ signal CD47 on cancer cells, limits cytotoxicity, forming a mechanism of resistance towards anti-cancer antibody therapeutics. In fact, tumor cells often overexpress CD47, thereby even more strongly restricting neutrophil-mediated tumor killing. Blocking the CD47-SIRPα interaction may therefore potentiate neutrophil-mediated antibody-dependent cellular cytotoxicity (ADCC) towards cancer cells, and various inhibitors of the CD47-SIRPα axis are now in clinical studies. Here, we review the role of neutrophils in antibody therapy in cancer and their regulation by the CD47-SIRPα innate immune checkpoint. Moreover, initial results of CD47-SIRPα blockade in clinical trials are discussed.

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Section: Neutrophils and Their Role In Cancermentioning

confidence: 99%

Targeting the CD47-SIRPα Innate Immune Checkpoint to Potentiate Antibody Therapy in Cancer by Neutrophils

Behrens

Berg

Egmond

2022

Cancers

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“…[ 60 ] Neutrophils can have both pro-tumorigenic and anti-tumorigenic effects depending on various factors, including the specific breast cancer subtype and the stage of the disease. [ 61 ] Neutrophils are recruited to the tumor site through chemotactic signals. [ 62 ] Tumor and stromal cells release chemokines (such as CXCL1, CXCL2, and CXCL8) that attract neutrophils to the tumor microenvironment.…”

Section: Mechanisms and Signaling Pathways Of Neutrophils In Breast C...mentioning

confidence: 99%

Exploring neutrophil functionality in breast cancer progression: A review

Obeagu,

Obeagu

2024

Medicine

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Breast cancer remains a pressing global health concern, with a myriad of intricate factors contributing to its development, progression, and heterogeneity. Among these multifaceted elements, the role of immune cells within the tumor microenvironment is gaining increasing attention. In this context, neutrophils, traditionally regarded as the first responders to infections, are emerging as noteworthy participants in the complex landscape of breast cancer. This paper seeks to unravel the intricate and multifaceted role of neutrophils in breast cancer. Neutrophils, classically known for their phagocytic and pro-inflammatory functions, are now recognized for their involvement in promoting or restraining tumor growth. While their presence within the tumor microenvironment may exert antitumor effects through immune surveillance and cytotoxic activities, these innate immune cells can also facilitate tumor progression by fostering an immunosuppressive milieu, promoting angiogenesis, and aiding metastatic dissemination. The intricacies of neutrophil-tumor cell interactions, signaling pathways, and mechanisms governing their recruitment to the tumor site are explored in detail. Challenges and gaps in current knowledge are acknowledged, and future directions for research are outlined. This review underscores the dynamic and context-dependent role of neutrophils in breast cancer and emphasizes the significance of unraveling their multifaceted contributions. As we delve into the complexities of the immune landscape in breast cancer, a deeper understanding of the warriors within, the neutrophils, presents exciting prospects for the development of novel therapeutic strategies and a more comprehensive approach to breast cancer management.

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“…Later on, the dysregulation of neutrophil chemotaxis as well as activation is found to contribute to multiple diseases, including cancer. 72 , 73 Of note, a larger number of tumor-infiltrating neutrophils maintaining the tumor immune microenvironment are significantly associated with worse outcome and prognosis of different cancers, as exemplified by CRC. 74 , 75 In hindsight, considering that whether tumor-infiltrating neutrophils are involved in cancer-related neuropathic pain remains poorly understood, this subchapter would discuss a limited number of preliminary experimental studies here, in order to give some indications for future research in this field.…”

Section: The Involvement Of Immune Cells In Cancer-related Neuropathi...mentioning

confidence: 99%

Contribution of immune cells to cancer-related neuropathic pain: An updated review

Pan

Lai

et al. 2023

Mol Pain

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Given that the incidence of cancer is dramatically increasing nowadays, cancer-related neuropathic pain including tumor-related and therapy-related pain gradually attracts more attention from researchers, which basically behaves as a metabolic-neuro-immune disorder with worse clinical outcomes and prognosis. Among various mechanisms of neuropathic pain, the common underlying one is the activation of inflammatory responses around the injured or affected nerve(s). Innate and adaptive immune reactions following nerve injury together contribute to the regulation of pain. On the other hand, the tumor immune microenvironment involving immune cells, as exemplified by lymphocytes, macrophages, neutrophils and dendritic cells, inflammatory mediators as well as tumor metastasis have added additional characteristics for studying the initiation and maintenance of cancer-related neuropathic pain. Of interest, these immune cells in tumor microenvironment exert potent functions in promoting neuropathic pain through different signaling pathways. To this end, this review mainly focuses on the contribution of different types of immune cells to cancer-related neuropathic pain, aims to provide a comprehensive summary of how these immune cells derived from the certain tumor microenvironment participate in the pathogenesis of neuropathic pain. Furthermore, the clarification of roles of various immune cells in different tumor immune microenvironments associated with certain cancers under neuropathic pain states constitutes innovative biology that takes the pain field in a different direction, and thereby provides more opportunities for novel approaches for the prevention and treatment of cancer-related neuropathic pain.

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Role of Tumor-Associated Neutrophils in the Molecular Carcinogenesis of the Lung

Cited by 12 publications

References 108 publications

Targeting the CD47-SIRPα Innate Immune Checkpoint to Potentiate Antibody Therapy in Cancer by Neutrophils

Targeting the CD47-SIRPα Innate Immune Checkpoint to Potentiate Antibody Therapy in Cancer by Neutrophils

Exploring neutrophil functionality in breast cancer progression: A review

Contribution of immune cells to cancer-related neuropathic pain: An updated review

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