The innate immune architecture of lung tumors and its implication in disease progression

Abstract

Lung malignancies are the leading cause of cancer-related mortality. By virtue of its unique physiological function, the lung microenvironment is highly dynamic and constantly subjected to mechanical, chemical and pathogenic stimuli. Thus, the airways rely on highly organized innate defense mechanisms to rapidly protect against pathogens and maintain pulmonary homeostasis. However, in the context of lung malignancy, these defenses often provide collateral inflammatory insults that can foster tumor progression. This review summarizes the interactions between cancer cells, recruited immune cells and tissue-resident cell subpopulations, such as airway epithelial cells and alveolar macrophages, during homeostasis and disease. Furthermore, we examine the role of the lung immune landscape in response to current therapeutic interventions for cancer. Given the prevalence of lung malignancies, we propose that consideration of lung physiology as a whole is necessary to understand and treat these lethal diseases. PerspectiveA broad understanding of the lung TIME could help identify new targets to enhance therapeutic efficacy of both cytotoxic and immune-targeted treatments [183]. In addition to the various cell types and immunoregulatory processes discussed here, many additional microenvironmental cell types in the lung contribute to disease progression, such as adaptive

Myeloid-derived suppressor cells—new and exciting players in lung cancer

“…Recent studies have increasingly emphasized the role of the TIME in the treatment of resistance. Immunosuppressive cells, such as bone marrow-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), and regulatory T (Treg) cells, act as suppressive TIME components to attenuate immune responses [2]. Among these cells, MDSCs have roles in the prognosis, development, and treatment of LC that have been paid increasing attention [3,4].…”

Insights Into Lung Cancer Immune-Based Biology, Prevention, and Treatment

“…A deeper scrutiny of PML microenvironment is also now possible when applying the high-resolution and multidimensional genetic, molecular, and cellular immunogenomic techniques probed in late stage cancers, to lung PMLs and their surrounding microenvironment. Not only will the anticipated findings add to the breadth of the currently known map of lung cancer evolution, but it may also challenge us to re-evaluate certain concepts, particularly since immunogenomic signatures of the lung are operative in PMLs and may thus dynamically modulate classically described molecular aberrations (269,270). Pan-institutional efforts such as pre-cancer atlases are heavily involved in supporting such research directions, by coordinating access to clinical data as well as standardizing research directed toward constructing comprehensive and multidimensional human tumor atlases.…”

Recent Advances in Pathology: the 2019 Annual Review Issue of The Journal of Pathology

“…In this Issue, we have three reviews that deal with very different aspects of this broad field. First, Daniela Quail and colleagues review the role of the innate immune system in lung malignancies, including metastasis to the lung . They summarise the interactions of tumour cells with recruited and tissue‐resident immune cells, including roles for the lung microbiome, tumour‐derived exosomes, neutrophil extracellular traps, myeloid‐derived suppressor cells and the intersections between innate and adaptive immunity.…”

“…They summarise the interactions of tumour cells with recruited and tissue‐resident immune cells, including roles for the lung microbiome, tumour‐derived exosomes, neutrophil extracellular traps, myeloid‐derived suppressor cells and the intersections between innate and adaptive immunity. They also provide an update on ongoing phase I, II and III clinical trials targeting different elements of the lung tumour environment . The review from Alan Melcher and colleagues deals with the dual effects of conventional genotoxic therapies on immune modulation.…”