PLD4 promotes M1 macrophages to perform antitumor effects in colon cancer cells

Gao, Long; Zhou, Yan; Zhou, Shuxian; Yu, Xian-Jing; Xu, Jing; Zuo, Luo; Luo, Yong-Hui; Li, Xiao-an

doi:10.3892/or.2016.5216

Cited by 36 publications

(24 citation statements)

References 31 publications

(37 reference statements)

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“…This suggested that the pro-inflammatory cytokines produced by macrophages could enhance the transcription activity of tumor cells and promote the growth of colon cancer cells. 23,24 Their results demonstrated that monocytes and macrophages promoted colon cancer cell growth, which was consistent with our findings that increased monocytes infiltration as well as macrophages were associated with poor prognosis of colon cancer.…”

Section: Discussionsupporting

confidence: 90%

<p>Significance of Tumor-Infiltrating Immune Cells in the Prognosis of Colon Cancer</p>

Ding

Wang

et al. 2020

OTT

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Increasing evidence has indicated an association between immune infiltration in colon cancer and clinical outcomes. The aim of this research is to comprehensively investigate the effect of 22 tumor-infiltrating immune cells (TIICs) on the prognosis of colon cancer patients. Methods: In our research, CIBERSORT algorithm was used to calculate the proportion of 22 TIICs in 369 colon cancer cases and 39 normal cases from the TCGA cohort. Cox regression analysis was used to analyze the effect of 22 TIICs on the prognosis of colon cancer. Immune risk scoring model was constructed based on the statistical correlation between TIICs subpopulation and survival. Meanwhile, multivariate Cox regression analysis was utilized to investigate whether the immune risk score model was an independent factor for predicting the prognosis of colon cancer. Nomogram was constructed to comprehensively predict the survival rate of colon cancer. P< 0.05 was considered to be statistically significant. Results: The results of the difference analysis showed that except for 12 TIICs, the remaining immune cells exhibited no differential infiltration between normal and colon cancer tissues (p<0. 05). Univariate Cox regression analysis revealed 5 immune cells statistically correlated with colon cancer-related survival risk, including B cells naive, B cells memory, monocytes, macrophages M0, macrophages M1 (P<0.05). In addition, a four-cell based immune risk scoring model was constructed through LASSO Cox regression analysis. KM curve indicated that patients in highrisk were associated with poor outcomes (p<0.001). ROC curve indicated that the immune risk score model was reliable in predicting survival risk (AUC=0.848). Our model showed satisfying AUC and survival correlation in the validation dataset (3-year over survival (OS) AUC=0.941, 5-year OS AUC=0.865, P=0.022). Furthermore, multivariate Cox regression analysis confirmed that the immune risk score model was an independent factor for predicting the prognosis of colon cancer (hazard ratio (HR) =5.017, 95% confidence interval (CI) =2.336-10.777; P<0.001). Ultimately, a nomogram was established to comprehensively predict the survival of colon cancer patients with the results of multivariate Cox regression analysis. Conclusion: Collectively, tumor-infiltrating immune cells played an essential role in the prognosis of colon cancer. Furthermore, immune risk score was an independent predictive factor of colon cancer, indicating a poor survival.

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Section: Discussionsupporting

confidence: 90%

<p>Significance of Tumor-Infiltrating Immune Cells in the Prognosis of Colon Cancer</p>

Ding

Wang

et al. 2020

OTT

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“…Amoeboid microglia were observed in PLP-overexpressing mice although MiDM in EAE onset bore processes 5 . Inflammation-associated genes were upregulated in MDM rather than MiDM in EAE 5 , whereas inflammatory reactions including phospholipase D4 (PLD4), involved in M1 macrophage polarization, was induced in reactive microglia of PLP-tg mice 47, 48 . However, the limitation of this study is the different brain regions analyzed in different models in order to observe microglial reactions in demyelinated white matter.…”

Section: Discussionmentioning

confidence: 99%

“…TLR4 has been implicated in pathophysiology of EAE 49, 50 . Although involvement of TLR4 is not well understood in the demyelination by PLP overexpression, previous reports suggested that PLD4, involved in M1 macrophage polarization, was induced both in LPS-stimulated primary microglial cultures and in the demyelination model by PLP overexpression 47, 48 . Thus, it is possible that microglial reactions in PLP-tg and after LPS stimulation at least partly share common signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

Polymorphic regulation of mitochondrial fission and fusion modifies phenotypes of microglia in neuroinflammation

Katoh

Nguyen

et al. 2017

Sci Rep

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Microglia are the resident macrophages of the central nervous system and play complex roles in the milieu of diseases including the primary diseases of myelin. Although mitochondria are critical for cellular functions and survival in the nervous system, alterations in and the roles of mitochondrial dynamics and associated signaling in microglia are still poorly understood. In the present study, by combining immunohistochemistry and 3D ultrastructural analyses, we show that mitochondrial fission/fusion in reactive microglia is differentially regulated from that in monocyte-derived macrophages and the ramified microglia of normal white matter in myelin disease models. Mouse cerebral microglia in vitro demonstrated that stimulation of TLR4 with lipopolysaccharide, widely used to examine microglial reactions, caused the activation of the mitochondrial fission protein, dynamin-related protein 1 (Drp1) and enhanced production of reactive oxygen species (ROS). The increase in the ROS level activated 5′ adenosine monophosphate-activated protein kinase (AMPK), and facilitated elongation of mitochondria along the microtubule tracks. These results suggest that the polymorphic regulation of mitochondrial fission and fusion in reactive microglia is mediated by distinct signaling under inflammatory conditions, and modulates microglial phenotypes through the production of ROS.

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“…This ability of PG2 to modulate tumoral M1/M2 polarization with preferential enhancement of M1 polarization is of clinical relevance, considering current experimental and clinical evidence indicating that M1 macrophages suppress tumorigenicity, decrease the viability and proliferation of cancer cells, and enhance the sensitivity of cancer cells to chemotherapy [37,38]. Additionally, two other studies, regardless of using host-produced histidine-rich glycoprotein (HRG) or phospholipase D4 (PLD4), have also implied the potential utility of M1 polarization as an effective anticancer therapeutic tool [39,40]. Thus, this PG2-induced depletion of M2 MDMs constitutes a potential new modality in immune-based anticancer therapy for patients with NSCLC.…”

Section: Discussionmentioning

confidence: 99%

Astragalus polysaccharides (PG2) Enhances the M1 Polarization of Macrophages, Functional Maturation of Dendritic Cells, and T Cell-Mediated Anticancer Immune Responses in Patients with Lung Cancer

et al. 2019

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Background: Recently, we demonstrated that Astragalus polysaccharide (PG2), the active ingredient in dried roots of astragalus membranaceus, ameliorates cancer symptom clusters and improves quality of life (QoL) in patients with metastatic disease by modulating inflammatory cascade against the background roles of inflammatory cells, including macrophages, dendritic cells (DCs), and cytotoxic T lymphocytes (CTLs) in tumor initiation, metastasis, and progression. Nevertheless, the role of PG2 in the modulation of anticancer immunogenicity and therapeutic response remains relatively underexplored and unclear. Purpose: The present study investigates how and to what extent PG2 modulates cellular and biochemical components of the inflammatory cascade and enhances anticancer immunity, as well as the therapeutic implication of these bio-events in patients with lung cancer. Methods and Results: Herein, we demonstrated that PG2 significantly increased the M1/M2 macrophage polarization ratio in non-small cell carcinoma (NSCLC) H441 and H1299 cells. This PG2-induced preferential pharmacologic up-regulation of tumoral M1 population in vitro positively correlated with the downregulation of tumor-promoting IL-6 and IL-10 expression in NSCLC cell-conditioned medium, with concomitant marked inhibition of cell proliferation, clonogenicity, and tumorsphere formation. Our ex vivo results, using clinical sample from our NSCLC cohort, demonstrated that PG2 also promoted the functional maturation of DCs with consequent enhancement of T cell-mediated anticancer immune responses. Consistent with the in vitro and ex vivo results, our in vivo studies showed that treatment with PG2 elicited significant time-dependent depletion of the tumor-associated M2 population, synergistically enhanced the anti-M2-based anticancer effect of cisplatin, and inhibited xenograft tumor growth in the NSCLC mice models. Moreover, in the presence of PG2, cisplatin-associated dyscrasia and weight-loss was markedly suppressed. Conclusion: These results do indicate a therapeutically-relevant role for PG2 in modulating the M1/M2 macrophage pool, facilitating DC maturation and synergistically enhancing the anticancer effect of conventional chemotherapeutic agent, cisplatin, thus laying the foundation for further exploration of the curative relevance of PG2 as surrogate immunotherapy and/or clinical feasibility of its use for maintenance therapy in patients with lung cancer.

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PLD4 promotes M1 macrophages to perform antitumor effects in colon cancer cells

Cited by 36 publications

References 31 publications

<p>Significance of Tumor-Infiltrating Immune Cells in the Prognosis of Colon Cancer</p>

<p>Significance of Tumor-Infiltrating Immune Cells in the Prognosis of Colon Cancer</p>

Polymorphic regulation of mitochondrial fission and fusion modifies phenotypes of microglia in neuroinflammation

Astragalus polysaccharides (PG2) Enhances the M1 Polarization of Macrophages, Functional Maturation of Dendritic Cells, and T Cell-Mediated Anticancer Immune Responses in Patients with Lung Cancer

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