Signaling of Macrophages that Contours the Tumor Microenvironment for Promoting Cancer Development

Messex, Justin K.; Byrd, Crystal; Liou, Geou-Yarh

doi:10.3390/cells9040919

Cited by 16 publications

(11 citation statements)

References 83 publications

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“…Of the 593 shared DEmRNAs, 577 were upregulated, accounting for 97.3%; thus, we mainly focused on their biological functions. The results indicated that many of them were associated with TME-related processes, such as the immune response, leukocyte migration, antigen binding, and the CAM pathway ( Harjunpaa et al, 2019 ; Cao et al, 2020 ; Messex et al, 2020 ; Sulea et al, 2020 ). Next, ceRNA and PPI networks were constructed.…”

Section: Discussionmentioning

confidence: 99%

Identification of Tumor Microenvironment-Related Prognostic Biomarkers in Luminal Breast Cancer

et al. 2020

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Background: The tumor microenvironment (TME) has been reported to have significant value in the diagnosis and prognosis of cancers. This study aimed to identify key biomarkers in the TME of luminal breast cancer (BC).Methods: We obtained immune scores (ISs) and stromal scores (SSs) for The Cancer Genome Atlas (TCGA) luminal BC cohort from the online ESTIMATE (Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data) portal. The relationships between ISs and SSs and the overall survival of luminal BC patients were assessed by the Kaplan-Meier method. The differentially expressed messenger RNAs (DEmRNAs) related to the ISs and SSs were subjected to functional enrichment analysis. Additionally, a competing endogenous RNA (ceRNA) network was constructed with differentially expressed microRNAs (DEmiRNAs) and long noncoding RNAs (DElncRNAs). Furthermore, a protein–protein interaction (PPI) network was established to analyze the DEmRNAs in the ceRNA network. Then, survival analysis of biomarkers involved in the ceRNA network was carried out to explore their prognostic value. Finally, these biomarkers were validated using the luminal BC dataset from the Gene Expression Omnibus (GEO) database.Results: The results showed that ISs were significantly associated with longer survival times of luminal BC patients. Functional enrichment analysis showed that the DEmRNAs were mainly associated with immune response, antigen binding, and the extracellular region. In the PPI network, the top 10 DEmRNAs were identified as hub genes that affected the TME of luminal BC. Finally, two DEmiRNAs, two DElncRNAs, and 17 DEmRNAs of the ceRNA network associated with the TME were shown to have prognostic value. Subsequently, the expression of 15 prognostic biomarkers was validated in one additional dataset (GSE81002). In particular, one lncRNA (GVINP1) and five mRNAs (CCDC69, DOCK2, IKZF1, JCHAIN, and NCKAP1L) were novel biomarkers.Conclusions: Our studies demonstrated that ISs were associated with the survival of luminal BC patients, and a set of novel biomarkers that might play a prognostic role in the TME of luminal BC was identified.

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Section: Discussionmentioning

confidence: 99%

Identification of Tumor Microenvironment-Related Prognostic Biomarkers in Luminal Breast Cancer

et al. 2020

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“…A key determinant of host antitumor immunity is the balance of i.t. M1 (tumoricidal) ( 29 ) and M2 (tumorigenic) ( 30 ) macrophages ( 31 ). i.t.…”

Section: Resultsmentioning

confidence: 99%

Intratumoral injection of schwannoma with attenuated Salmonella typhimurium induces antitumor immunity and controls tumor growth

Ahmed

Oliva

Shao

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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Schwannomas are slow-growing benign neoplasms that develop throughout the body causing pain, sensory/motor dysfunction, and death. Because bacterial immunotherapy has been used in the treatment of some malignant neoplasms, we evaluated attenuated Salmonella typhimurium strains as immunotherapies for benign murine schwannomas. Several bacterial strains were tested, including VNP20009, a highly attenuated strain that was previously shown to be safe in human subjects with advanced malignant neoplasms, and a VNP20009 mutant that was altered in motility and other properties that included adherence and invasion of cultured mammalian cells. VNP20009 controlled tumor growth in two murine schwannoma models and induced changes in cytokine and immune effector cell profiles that were consistent with induction of enhanced innate and adaptive host immune responses compared with controls. Intratumoral (i.t.) injection of S. typhimurium led to tumor cell apoptosis, decreased tumor angiogenesis, and lower growth of the injected schwannoma tumors. Invasive VNP20009 was significantly more efficacious than was a noninvasive derivative in controlling the growth of injected tumors. Bacterial treatment apparently induced systemic antitumor immunity in that the growth of rechallenge schwannomas implanted following primary bacterial treatment was also reduced. Checkpoint programmed death-1 (PD-1) blockade induced by systemic administration of anti–PD-1 antibodies controlled tumor growth to the same degree as i.t. injection of S. typhimurium , and together, these two therapies had an additive effect on suppressing schwannoma growth. These experiments represent validation of a bacterial therapy for a benign neoplasm and support development of S. typhimurium VNP20009, potentially in combination with PD-1 inhibition, as a schwannoma immunotherapy.

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“…M1 macrophages, stimulated by LPS and interferon gamma, are identified by their production of high levels of pro‐inflammatory cytokines and promotion of the Th1 response in the adaptive immune response. M2 macrophages are activated by IL‐4 or IL‐13 ligands and notably polarized into M2a (anti‐inflammatory, tissue remodelling), M2b (Th2 activation, immunoregulation), M2c (phagocytosis of apoptotic cells), M2d (angiogenesis, tumour progression) subtypes, which are response for tumour progression and the main population of macrophages in TME 43 . IL‐10, IL‐4, IL‐13, CCL2, CCL3, CCL4, CCL5 and MFG‐E8 in TME promote M2 macrophages generation.…”

Section: Composition and Function Of The Tmementioning

confidence: 99%

Modifying the tumour microenvironment and reverting tumour cells: New strategies for treating malignant tumours

et al. 2020

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The tumour microenvironment (TME) plays a pivotal role in tumour fate determination. The TME acts together with the genetic material of tumour cells to determine their initiation, metastasis and drug resistance. Stromal cells in the TME promote the growth and metastasis of tumour cells by secreting soluble molecules or exosomes. The abnormal microenvironment reduces immune surveillance and tumour killing. The TME causes low anti‐tumour drug penetration and reactivity and high drug resistance. Tumour angiogenesis and microenvironmental hypoxia limit the drug concentration within the TME and enhance the stemness of tumour cells. Therefore, modifying the TME to effectively attack tumour cells could represent a comprehensive and effective anti‐tumour strategy. Normal cells, such as stem cells and immune cells, can penetrate and disrupt the abnormal TME. Reconstruction of the TME with healthy cells is an exciting new direction for tumour treatment. We will elaborate on the mechanism of the TME to support tumours and the current cell therapies for targeting tumours and the TME—such as immune cell therapies, haematopoietic stem cell (HSC) transplantation therapies, mesenchymal stem cell (MSC) transfer and embryonic stem cell‐based microenvironment therapies—to provide novel ideas for producing breakthroughs in tumour therapy strategies.

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Signaling of Macrophages that Contours the Tumor Microenvironment for Promoting Cancer Development

Cited by 16 publications

References 83 publications

Identification of Tumor Microenvironment-Related Prognostic Biomarkers in Luminal Breast Cancer

Identification of Tumor Microenvironment-Related Prognostic Biomarkers in Luminal Breast Cancer

Intratumoral injection of schwannoma with attenuated Salmonella typhimurium induces antitumor immunity and controls tumor growth

Modifying the tumour microenvironment and reverting tumour cells: New strategies for treating malignant tumours

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