LYVE1+ macrophages of murine peritoneal mesothelium promote omentum-independent ovarian tumor growth

Zhang, Nan; Kim, Seung Hyeon; Gainullina, Anastasiia; Erlich, Emma; Onufer, Emily J.; Kim, Jiseon; Czepielewski, Rafael S.; Helmink, Beth A.; Dominguez, Joseph R; Saunders, Brian T.; Ding, Jie; Williams, Jesse W.; Jiang, Jean X.; Segal, Brahm H.; Zinselmeyer, Bernd H.; Randolph, Gwendalyn J.; Kim, Ki Wook

doi:10.1084/jem.20210924

Cited by 50 publications

(52 citation statements)

References 74 publications

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“…To answer this question, we crossed Lyve1-Cre mice to CSF1R flox/flox mice (termed Lyve1 ΔCSF1R ), to specifically delete the CSF1R gene in LYVE1-expressing cells. As CSF1R signaling is known to be required for macrophage differentiation and survival, this mouse results in selective Lyve1 + macrophage loss, as previously shown for macrophages (Zhang et al, 2021). In pancreas tissues, we also observed a significant reduction in LYVE1 + macrophages in Lyve1 ΔCSF1R mice compared to Lyve1-Cre (-) littermate controls (Supp.…”

Section: Tissue-resident Macrophages Are Required For Shaping the Tis...supporting

confidence: 83%

“…These data show, on average, embryonic tissue resident macrophages have district phenotypes with likely enhanced tissue remodeling properties that are retained during tissue injury. Notably, these phenotypes are similar to reports in other tissues (Casanova-Acebes et al ., 2021; Dick et al ., 2022; Zhang et al ., 2021; Zhu et al ., 2017).…”

Section: Resultsmentioning

confidence: 99%

“…Several studies have shown that ontogeny of TRMs can influence their phenotype and specific function (Bowman et al, 2016; Casanova-Acebes et al ., 2021; Loyher et al ., 2018; Zhang et al ., 2021; Zhu et al ., 2017). To investigate the ontogeny-dependent roles of macrophages during pancreas injury by pancreatitis or tumor formation, we first performed RNAseq analysis of macrophages sorted from Flt3-YFP mice treated with either vehicle, acute cerulein, or orthotopically implanted PDAC tumors.…”

Section: Resultsmentioning

confidence: 99%

“…Further, we identify a subset of TRMs that are primarily derived from embryonic progenitors and are marked as Lyve1 Hi Cx3cr1 Lo MHCII Lo . Other macrophage populations display mixed origin and are marked as Lyve1 Lo Cx3cr1 Hi MHCII Hi , agreeing with the dichotomy of marker expression by TRM populations that have been established across fat, dermis, heart, lung, mesenteric membranes, and other tissues (Chakarov et al ., 2019; Dick et al ., 2022; Gibbings et al, 2017; Lim et al ., 2018; Zhang et al ., 2021). Additionally, these other studies on Lyve1 Hi MHCII Lo TRMs in the lung, arteries, and mesenteric membranes report their involvement in extracellular matrix deposition and remodeling, and display a strikingly similar transcriptional profile as Lyve1 Hi MHCII Lo macrophages reported here in the pancreas.…”

Section: Discussionmentioning

confidence: 99%

“…TRMs have been implicated in a wide variety of roles in maintaining tissue homeostasis, extracellular matrix (ECM) remodeling, and inflammation (Ginhoux and Jung, 2014). Additionally, across the fat, dermis, heart, lung, and mesenteric membranes, a dogma has emerged that interstitial TRMs can be subdivided into at least two major subpopulations, Lyve1 Hi CX3CR1 Lo MHCII Lo or Lyve1 Lo CX3CR1 Hi MHCII Hi subsets, with multiple reports now implicating Lyve1 Hi CX3CR1 Lo MHCII Lo TRMs as being involved in ECM remodeling (Chakarov et al, 2019; Dick et al, 2022; Lim et al, 2018; Zhang et al, 2021). However, it is not fully understood how TRM subsets and MDMs might be uniquely poised to respond to tissue damage or pathologic conditions and how their responses might differ.…”

Section: Introductionmentioning

confidence: 99%

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Pancreas resident macrophage-induced fibrosis has divergent roles in pancreas inflammatory injury and PDAC

Baer

Zuo

Kang

et al. 2022

Preprint

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Tissue-resident macrophages (TRMs) are long-lived cells that maintain locally and can be phenotypically distinct from monocyte-derived macrophages (MDMs). However, whether TRMs and MDMs have functional distinction under differing pathologies is not understood. Here, we show a significant portion of macrophages that accumulated during pancreatitis and pancreatic cancer were expanded from TRMs. We further established that pancreas TRMs have a distinct extracellular matrix remodeling phenotype that was critical for maintaining tissue homeostasis during inflammation. Loss of TRMs led to exacerbation of severe pancreatitis and animal death, due to impaired acinar cell survival and recovery. In pancreatitis, TRMs elicited protective effects by triggering the accumulation and activation of fibroblasts, which was necessary for initiating fibrosis as a wound healing response. The same TRM-driven fibrosis, however, drove pancreas cancer pathogenesis and progression. Together, these findings indicate that TRMs play divergent roles in the pathogenesis of pancreatitis and cancer through regulation of stromagenesis.

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Section: Tissue-resident Macrophages Are Required For Shaping the Tis...supporting

confidence: 83%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Pancreas resident macrophage-induced fibrosis has divergent roles in pancreas inflammatory injury and PDAC

Baer

Zuo

Kang

et al. 2022

Preprint

Self Cite

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Mouse Tissue‐Resident Peritoneal Macrophages in Homeostasis, Repair, Infection, and Tumor Metastasis

et al. 2023

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Large peritoneal macrophages (LPMs) are long-lived, tissue-resident macrophages, formed during embryonic life, developmentally and functionally confined to the peritoneal cavity. LPMs provide the first line of defense against life-threatening pathologies of the peritoneal cavity, such as abdominal sepsis, peritoneal metastatic tumor growth, or peritoneal injuries caused by trauma, or abdominal surgery. Apart from their primary phagocytic function, reminiscent of primitive defense mechanisms sustained by coelomocytes in the coelomic cavity of invertebrates, LPMs fulfill an essential homeostatic function by achieving an efficient clearance of apoptotic, that is crucial for the maintenance of self-tolerance. Research performed over the last few years, in mice, has unveiled the mechanisms by which LPMs fulfill a crucial role in repairing peritoneal injuries and controlling microbial and parasitic infections, reflecting that the GATA6-driven LPM transcriptional program can be modulated by extracellular signals associated with pathological conditions. In contrast, recent experimental evidence supports that peritoneal tumors can subvert LPM metabolism and function, leading to the acquisition of a tumor-promoting potential. The remarkable functional plasticity of LPMs can be nevertheless exploited to revert tumor-induced LPM protumor potential, providing the basis for the development of novel immunotherapeutic approaches against peritoneal tumor metastasis based on macrophage reprogramming.

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Tissue‐Resident Macrophages in Cancer: Friend or Foe?

Chi,

Gao,

Liu

2024

Cancer Medicine

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IntroductionMacrophages are essential in maintaining homeostasis, combating infections, and influencing the process of various diseases, including cancer. Macrophages originate from diverse lineages: Notably, tissue‐resident macrophages (TRMs) differ from hematopoietic stem cells and circulating monocyte‐derived macrophages based on genetics, development, and function. Therefore, understanding the recruited and TRM populations is crucial for investigating disease processes.MethodsBy searching literature databses, we summarized recent relevant studies. Research has shown that tumor‐associated macrophages (TAMs) of distinct origins accumulate in tumor microenvironment (TME), with TRM‐derived TAMs closely resembling gene signatures of normal TRMs.ResultsRecent studies have revealed that TRMs play a crucial role in cancer progression. However, organ‐specific effects complicate TRM investigations. Nonetheless, the precise involvement of TRMs in tumors is unclear. This review explores the multifaceted roles of TRMs in cancer, presenting insights into their origins, proliferation, the latest research methodologies, their impact across various tumor sites, their potential and strategies as therapeutic targets, interactions with other cells within the TME, and the internal heterogeneity of TRMs.ConclusionsWe believe that a comprehensive understanding of the multifaceted roles of TRMs will pave the way for targeted TRM therapies in the treatment of cancer.

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LYVE1+ macrophages of murine peritoneal mesothelium promote omentum-independent ovarian tumor growth

Cited by 50 publications

References 74 publications

Pancreas resident macrophage-induced fibrosis has divergent roles in pancreas inflammatory injury and PDAC

Pancreas resident macrophage-induced fibrosis has divergent roles in pancreas inflammatory injury and PDAC

Mouse Tissue‐Resident Peritoneal Macrophages in Homeostasis, Repair, Infection, and Tumor Metastasis

Tissue‐Resident Macrophages in Cancer: Friend or Foe?

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