Emerging and multifaceted role of neutrophils in lung cancer

Aloe, Christian; Wang, Hao; Vlahos, Ross; Irving, Louis; Steinfort, Daniel; Bozinovski, Steven

doi:10.21037/tlcr-20-760

Cited by 51 publications

(37 citation statements)

References 106 publications

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“…Kargl et al, found that neutrophil content in the TME negatively correlated with the presence of CD8+ and CD4+ T cells and with Th1 and Th17 subsets, but not with Treg cells, implicating a potential immune suppressive role for neutrophils in NSCLC (44,45). Data from preclinical studies in IL-17:K-Ras mutated transgenic mice demonstrated that resistance to anti-PD-1 therapy is abrogated by neutrophil depletion, reconstituting T cell activation (46).…”

Section: Immunosuppressionmentioning

confidence: 99%

Therapeutic Implications of Tumor Microenvironment in Lung Cancer: Focus on Immune Checkpoint Blockade

et al. 2022

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In the last decade, the treatment of non-small cell lung cancer (NSCLC) has been revolutionized by the introduction of immune checkpoint inhibitors (ICI) directed against programmed death protein 1 (PD-1) and its ligand (PD-L1), or cytotoxic T lymphocyte antigen 4 (CTLA-4). In spite of these improvements, some patients do not achieve any benefit from ICI, and inevitably develop resistance to therapy over time. Tumor microenvironment (TME) might influence response to immunotherapy due to its prominent role in the multiple interactions between neoplastic cells and the immune system. Studies investigating lung cancer from the perspective of TME pointed out a complex scenario where tumor angiogenesis, soluble factors, immune suppressive/regulatory elements and cells composing TME itself participate to tumor growth. In this review, we point out the current state of knowledge involving the relationship between tumor cells and the components of TME in NSCLC as well as their interactions with immunotherapy providing an update on novel predictors of benefit from currently employed ICI or new therapeutic targets of investigational agents. In first place, increasing evidence suggests that TME might represent a promising biomarker of sensitivity to ICI, based on the presence of immune-modulating cells, such as Treg, myeloid derived suppressor cells, and tumor associated macrophages, which are known to induce an immunosuppressive environment, poorly responsive to ICI. Consequently, multiple clinical studies have been designed to influence TME towards a pro-immunogenic state and subsequently improve the activity of ICI. Currently, the mostly employed approach relies on the association of “classic” ICI targeting PD-1/PD-L1 and novel agents directed on molecules, such as LAG-3 and TIM-3. To date, some trials have already shown promising results, while a multitude of prospective studies are ongoing, and their results might significantly influence the future approach to cancer immunotherapy.

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Section: Immunosuppressionmentioning

confidence: 99%

Therapeutic Implications of Tumor Microenvironment in Lung Cancer: Focus on Immune Checkpoint Blockade

et al. 2022

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“…The infiltration of phagocytes and Treg in tumors ultimately promotes tumor growth. The differentiation of TAN can be regulated by regulating cytokines and chemokines in the immune microenvironment, so that it mainly plays an anti-tumor effect in the liver immune microenvironment (28)(29)(30).…”

Section: Tumor-associated Neutrophilmentioning

confidence: 99%

Research Progress on the Microenvironment and Immunotherapy of Advanced Non-Small Cell Lung Cancer With Liver Metastases

Fang

2022

Front. Oncol.

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Lung cancer is a malignant tumor with the highest morbidity and mortality, and more than 75% of patients are diagnosed at an advanced stage. Liver metastases occur in 20% of non-small cell lung cancer patients, and their prognosis are poor. In recent years, immune checkpoint inhibitor monotherapy and combination therapy have made breakthrough progress in advanced Non-small cell lung cancer (NSCLC) patients. However, compared with the overall population, the liver metastases population was an independent prognostic factor for poor immunotherapy response. Whether and how immunotherapy can work in NSCLC patients with liver metastases is a major and unresolved challenge. Although more and more data have been disclosed, the research progress of NSCLC liver metastasis is still limited. How liver metastasis modulates systemic antitumor immunity and the drug resistance mechanisms of the liver immune microenvironment have not been elucidated. We systematically focused on non-small cell lung cancer patients with liver metastases, reviewed and summarized their pathophysiological mechanisms, immune microenvironment characteristics, and optimization of immunotherapy strategies.

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“…Neutrophils are the dominant type of immune cell in the NSCLC tumor microenvironment (TME), to which they respond and polarize into distinct phenotypes that operate in an anti-tumorigenic or pro-tumorigenic manner [ 43 ]. The clinically relevant adverse impact of a neutrophil predominance, both systemically and in the TME of patients with NSCLC, is exacerbated by the negative prognostic value of both a persistent neutrophilia and a high neutrophil-to-lymphocyte ratio (NLR ≥ 5) [ 44 ].…”

Section: Circulating Immune Cellsmentioning

confidence: 99%

Emerging Blood-Based Biomarkers for Predicting Immunotherapy Response in NSCLC

Oitaben

Fonseca

Villanueva

et al. 2022

Cancers

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Immunotherapy with Immune Checkpoint Inhibitors (ICIs) has demonstrated a profitable performance for Non-Small Cell Lung Cancer (NSCLC) cancer treatment in some patients; however, there is still a percentage of patients in whom immunotherapy does not provide the desired results regarding beneficial outcomes. Therefore, obtaining predictive biomarkers for ICI response will improve the treatment management in clinical practice. In this sense, liquid biopsy appears as a promising method to obtain samples in a minimally invasive and non-biased way. In spite of its evident potential, the use of these circulating biomarkers is still very limited in the real clinical practice, mainly due to the huge heterogeneity among the techniques, the lack of consensus, and the limited number of patients included in these previous studies. In this work, we review the pros and cons of the different proposed biomarkers, such as soluble PD-L1, circulating non-coding RNA, circulating immune cells, peripheral blood cytokines, and ctDNA, obtained from liquid biopsy to predict response to ICI treatment at baseline and to monitor changes in tumor and tumor microenvironment during the course of the treatment in NSCLC patients.

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Emerging and multifaceted role of neutrophils in lung cancer

Cited by 51 publications

References 106 publications

Therapeutic Implications of Tumor Microenvironment in Lung Cancer: Focus on Immune Checkpoint Blockade

Therapeutic Implications of Tumor Microenvironment in Lung Cancer: Focus on Immune Checkpoint Blockade

Research Progress on the Microenvironment and Immunotherapy of Advanced Non-Small Cell Lung Cancer With Liver Metastases

Emerging Blood-Based Biomarkers for Predicting Immunotherapy Response in NSCLC

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