Natural Killer Cells in Cancers of Respiratory System and Their Applications in Therapeutic Approaches

Our plain-English summary of Natural Killer Cells in Cancers of Respiratory System and Their Applications in Therapeutic Approaches, by M. Dokhanchi, A.P. Javaherdehi, M. Raad, et al (Immunity, Inflammation and Disease, 2024).

The study

• Authors: M. Dokhanchi, A.P. Javaherdehi, M. Raad, S. Khalilollah, P. Mahdavi, M.H. Razizadeh, A. Zafarani
• Journal: Immunity, Inflammation and Disease
• Published: 2024;12(11):e70079
• Type of article: Review
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Cancer is still regarded as a major worldwide health issue due to its high health and socioeconomic burden. Currently, lung cancer is the most common cause of cancer-related fatalities globally. Additionally, mesotheliomas and other cancers of the respiratory system, including those of the trachea, larynx, and bronchi, are also posing a significant health threat. Natural killer (NK) cells are lymphocytes of the innate immune system involved in response against cancer.

Objective: This review discussed recent findings in the context of NK cell activity in the immune surveillance of respiratory system cancers and NK cell-based treatments to combat those malignancies.

Results: The presence of natural killer cells in the tumor microenvironment is shown to be associated with a higher survival rate in patients with various malignancies. However, cancerous cells benefit from several mechanisms to evade natural killer cell-mediated cytotoxicity, including reduced major histocompatibility complex I expression, shedding of ligands, upregulation of inhibitory receptors, and release of soluble factors. Using NK cells to design therapeutic approaches may enhance antitumor immunity and improve clinical outcomes. Clinical trials investigating the use of natural killer cells in combination with cytokine stimulation or immune checkpoint inhibitors have exhibited promising results in various respiratory system malignancies.

Conclusion: Respiratory system cancers present significant health challenges worldwide, and while NK cells play a crucial role in tumor surveillance, tumors often evade NK cell responses through various mechanisms. Advances in NK cell-based therapies, including CAR-NK cells, immune checkpoint inhibitors, and cytokine stimulation, have shown promising outcomes in tackling these tactics. However, challenges such as the immunosuppressive tumor microenvironment persist. Ongoing research is crucial to improve NK cell therapies by targeting autophagy, modulating miRNAs, and developing combinatorial approaches to enhance treatment efficacy for respiratory cancers.

© 2024 The Author(s). Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.

In plain English

This article was a review, not a new study. The authors searched PubMed, Scopus and Google Scholar for studies published up to August 2024 on natural killer (NK) cells, a type of immune cell, in cancers of the respiratory system, including lung cancer, laryngeal cancer and mesothelioma. They described how NK cells attack tumors, how tumors evade them, and NK cell-based treatments. The review stated that mesotheliomas are associated with asbestos exposure. It summarized earlier research reporting that exposing NK cells to asbestos reduced their cell-killing (cytotoxic) activity and changed activating receptors such as NKG2D. It also cited research reporting that NK cells from mesothelioma patients showed reduced NKp46. It cited studies finding that survival in malignant pleural mesothelioma did not vary notably with NK cell density. Most of the research it reviewed concerned lung cancer. There, clinical trials combining NK cells with cytokine stimulation or checkpoint-inhibitor drugs were described as showing promising results. The authors concluded that NK cell-based approaches show promise but face obstacles such as the immunosuppressive tumor environment. They noted that respiratory cancers other than lung cancer need more study.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of published literature (no new data collected)
• Who was studied: English-language published studies of NK cell activity in respiratory system cancers (lung, trachea, larynx, bronchi, thoracic sarcomas, mesothelioma), found in PubMed, Scopus and Google Scholar up to August 2024 plus their reference lists; the number of included studies is not stated
• Exposure: Not an exposure study. Asbestos is discussed as associated with mesothelioma. The review also summarizes earlier research in which NK cells were exposed to asbestos. Fiber types are not specified.
• Main results:
  • Reviewed research (other studies) reported that exposing NK cells to asbestos reduced their cytotoxic activity and changed expression of activating receptors such as NKG2D
  • A reviewed study of mesothelioma patients reported that their NK cells showed reduced NKp46 expression, while NKG2D and 2B4 expression was normal
  • The review described reduced ERK1/2 phosphorylation in NK cells as one of the effects of asbestos, based on other studies
  • Reviewed studies found that survival in malignant pleural mesothelioma did not vary notably with NK cell density
  • A reviewed study reported that after the anti-CTLA-4 drug tremelimumab, NK cell subsets in mesothelioma patients returned to normal levels
  • A meta-analysis of 53 studies, cited by the review, associated NK cell infiltration with reduced mortality risk in solid tumors. Of its four lung cancer papers, two found an association between high NK cell infiltration and better overall survival, and two found no correlation.
  • A cited study of 109 patients with advanced NSCLC compared 55 patients given pembrolizumab plus NK cells with 54 given pembrolizumab alone, and reported enhanced survival with the combination
• The authors' conclusion: The authors concluded that combination therapies using NK cells with cytokine stimulation or immune checkpoint inhibitors have shown promising clinical trial results. They added that obstacles such as the immunosuppressive tumor microenvironment remain.
• Limitations the authors state:
  • Most studies in the field concerned lung cancer, so other respiratory system cancers have received less attention
  • How the causes of respiratory system cancers affect the resulting tumors as targets for NK cell therapies has not yet been studied

Topics

Medical terms in this study, explained in our Lexicon: Lung Cancer, Mesothelioma, Bronchus, Tumor Microenvironment, Clinical Trial, Cytokine, checkpoint inhibitors.

Related studies

• Potential treatment approaches for malignant peritoneal mesothelioma: in vivo and in vitro experimental study of natural killer cell immunotherapy — H. Wu, Y. Wang, et al. (2024)
• A Multimodal Framework to Guide Solid Tumor Indications for Natural Killer Cell-Based Therapy — L. Chiossone, V. Picant, et al. (2026)
• Asbestos and cancer: human natural killer cell activity is suppressed by asbestos fibers but can be restored by recombinant interleukin-2 — B.W. Robinson (1989)
• Functional Alteration of Natural Killer Cells and Cytotoxic T Lymphocytes upon Asbestos Exposure and in Malignant Mesothelioma Patients — Y. Nishimura, N. Kumagai-Takei, et al. (2015)
• Lymphocyte subsets in subjects exposed to asbestos: changes in circulating natural killer cells — N. al Jarad, M. Macey, et al. (1992)
• Natural killer cell activity in asbestos workers. Interactive effects of smoking and asbestos exposure — R.D. deShazo, J. Morgan, et al. (1988)

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