The tumor immunosuppressive microenvironment impairs the therapy of anti-HER2/neu antibody

Xu, Meng; Du, Xuexiang; Liu, Mingyue; Li, Sirui; Li, Xiaozhu; Fu, Yang–Xin; Wang, Shengdian

doi:10.1007/s13238-012-2044-3

Cited by 10 publications

(7 citation statements)

References 26 publications

(31 reference statements)

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“…Also CTL infiltration and IFN-γ-production in the tumor increased [5]. However, merely increasing the tumor infiltrating CTLs without removal of TAMs failed to reverse anti-HER2 resistance [70]. Also, blocking the interaction between CD47 and signal-regulatory protein alpha (SIRPα) may be a macrophage-mediated way to improve trastuzumab efficacy.…”

Section: Anti-her2 Targeted Therapymentioning

confidence: 99%

Tumor-associated macrophages in breast cancer: Innocent bystander or important player?

Qiu

Waaijer

Zwager

et al. 2018

Cancer Treatment Reviews

323

268

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Tumor-associated macrophages (TAMs) are important tumor-promoting cells in the breast tumor microenvironment. Preclinically TAMs stimulate breast tumor progression, including tumor cell growth, invasion and metastasis. TAMs also induce resistance to multiple types of treatment in breast cancer models. The underlying mechanisms include: induction and maintenance of tumor-promoting phenotype in TAMs, inhibition of CD8+ T cell function, degradation of extracellular matrix, stimulation of angiogenesis and inhibition of phagocytosis. Several studies reported that high TAM infiltration of breast tumors is correlated with a worse patient prognosis. Based on these findings, macrophage-targeted treatment strategies have been developed and are currently being evaluated in clinical breast cancer trials. These strategies include: inhibition of macrophage recruitment, repolarization of TAMs to an antitumor phenotype, and enhancement of macrophage-mediated tumor cell killing or phagocytosis. This review summarizes the functional aspects of TAMs and the rationale and current evidence for TAMs as a therapeutic target in breast cancer.

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Section: Anti-her2 Targeted Therapymentioning

confidence: 99%

Tumor-associated macrophages in breast cancer: Innocent bystander or important player?

Qiu

Waaijer

Zwager

et al. 2018

Cancer Treatment Reviews

323

268

View full text Add to dashboard Cite

show abstract

“…Considering that the in vitro inhibition of the BRAF downstream target MEK also affected MGL ligand expression, we assume that activating mutations in members of the MAPK pathway other than BRAF, such as KRAS and EGFR, may also cause aberrations in tumor cell glycosylation. In support of this hypothesis, high MGL-binding in breast carcinoma was recently associated with the expression of HER2/neu [ 32 ], which is an upstream activator of the MAPK-cascade and has been related to an immunosuppressive tumor microenvironment [ 33 ]. These findings suggest that various oncogenic alterations involved in activation of the MAPK pathway may participate in modulation of the tumor-related glycome.…”

Section: Discussionmentioning

confidence: 99%

MGL ligand expression is correlated to BRAF mutation and associated with poor survival of stage III colon cancer patients

et al. 2015

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“…Malignant tumor phenotypes, such as invasiveness, metastasis, drug resistance and poor prognosis, depend on both the distinct genetic and epigenetic characteristics of the tumor as well as other factors in the tumor microenvironment (Gandellini et al, 2015). The tumor microenvironment is composed of tumor cells, various types of stromal cells and the extracellular matrix, in which tumor cells and stromal cells interact by releasing a variety of cytokines, chemokines and growth factors (M. Xu et al, 2012). In recent years, it has become clear that tumor cells, as well as other cells and factors that accumulate in tumor-bearing hosts, play a critical role in patient outcomes (Schlößer et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Peer Review #1 of "Screening of immunosuppressive factors for biomarkers of breast cancer malignancy phenotypes and subtype-specific targeted therapy (v0.1)"

2019

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To screen and validate immunosuppressive factors in luminal-and basal-like breast cancer cell lines and tissue samples associated with malignant phenotypes. The mRNA microarray datasets, GSE40057 and GSE1561, were downloaded and remodelled, and differentially expressed genes (DEGs) were identified. Weighted Gene Co-expression Network Analysis (WGCNA) and Gene Ontology (GO) and KEGG pathway enrichment analysis were performed to explore the immune-related events that related to the basal-like trait. The online resources, GOBO, Kaplan-Meier Plotter and UALCAN, were employed to screen for immunosuppressive factors associated with breast cancer malignant phenotypes. Immunohistochemistry was used to evaluate VEGFA and MIF levels in breast tumours and normal breast tissues; qPCR and western blot were used to validate the expression of clinical immune-oncology (IO) therapeutic targets CD274 (PD-L1) and IL8 in cell lines. The results showed that there were varies immune-related events contribute to the trait of basal-like breast cancer. First, TGFβ1 and IL8 had higher average expression levels in more malignant cell lines; Second, MIF and VEGFA had higher average expression levels in more malignant breast cancer tissue, and the high expression levels of them were associated with poor survival rate. Third, IO targets CD274 and IL8 were confirmed that more suitable for the treatment of basal-like breast cancer. In view of the above, during the formation and development of breast cancer, immune-related genes are always activated, and immunosuppressive factors, IL8, TGFβ1, MIF and VEGFA are up-regulated. Such molecules could be used as biomarkers for breast cancer prognosis. However, because individual

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The tumor immunosuppressive microenvironment impairs the therapy of anti-HER2/neu antibody

Abstract: ABSTRACT

Cited by 10 publications

References 26 publications

Tumor-associated macrophages in breast cancer: Innocent bystander or important player?

Tumor-associated macrophages in breast cancer: Innocent bystander or important player?

MGL ligand expression is correlated to BRAF mutation and associated with poor survival of stage III colon cancer patients

Peer Review #1 of "Screening of immunosuppressive factors for biomarkers of breast cancer malignancy phenotypes and subtype-specific targeted therapy (v0.1)"

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