&lt;p&gt;M2 macrophages confer resistance to 5-fluorouracil in colorectal cancer through the activation of CCL22/PI3K/AKT signaling&lt;/p&gt;

Chen, Wei; Yang, Chaogang; Wang, Shuyi; Shi, Dongdong; Zhang, Chunxiao; Lin, Xiaobin; Xiong, Bin

doi:10.2147/ott.s198126

Cited by 77 publications

(72 citation statements)

References 39 publications

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“…CCL22 was found in macrophages of tongue squamous cell carcinoma [46]. Additionally, the secretion of CCL22 by M2-like macrophages in colorectal cancer was proven [32]. However, CCL22 expression in cervical cancer has not been previously determined.…”

Section: Discussionmentioning

confidence: 96%

Higher CCL22+ Cell Infiltration is Associated with Poor Prognosis in Cervical Cancer Patients

Wang

Schmoeckel

Kost

et al. 2019

Cancers

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The chemokine CCL22 recruits regulatory T (T-reg) cells into tumor tissues and is expressed in many human tumors. However, the prognostic role of CCL22 in cervical cancer (CC) has not been determined. This study retrospectively analyzed the clinical significance of the expression of CCL22 and FOXP3 in 230 cervical cancer patients. Immunohistochemical staining analyses of CCL22 and FOXP3 were performed with a tissue microarray. Double immunofluorescence staining, cell coculture, and ELISA were used to determine CCL22 expressing cells and mechanisms. The higher number of infiltrating CCL22+ cells (CCL22 high ) group was associated with lymph node metastasis (p = 0.004), Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stages (p = 0.010), therapeutic strategies (p = 0.007), and survival status (p = 0.002). The number of infiltrating CCL22+ cells was positively correlated with that of infiltrating FOXP3+ cells (r = 0.210, p = 0.001). The CCL22 high group had a lower overall survival rate (OS), compared to the CCL22 low group (p = 0.001). However, no significant differences in progression free survival (PFS) were noted between the two groups. CCL22 high was an independent predictor of shorter OS (HR, 4.985; p = 0.0001). The OS of the combination group CCL22 high FOXP3 high was significantly lower than that of the combination group CCL22 low FOXP3 low regardless of the FIGO stage and disease subtype. CCL22 high FOXP3 high was an independent indictor of shorter OS (HR, 5.284; p = 0.009). The PFS of group CCL22 high FOXP3 high was significantly lower than that of group CCL22 low FOXP3 low in cervical adenocarcinoma, but CCL22 high FOXP3 high was not an independent indicator (HR, 3.018; p = 0.068). CCL22 was primarily expressed in M2-like macrophages in CC and induced by cervical cancer cells. The findings of our study indicate that cervical cancer patients with elevated CCL22+ infiltrating cells require more aggressive treatment. Moreover, the results provide a basis for subsequent, comprehensive studies to advance the design of immunotherapy for cervical cancer.

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Section: Discussionmentioning

confidence: 96%

Higher CCL22+ Cell Infiltration is Associated with Poor Prognosis in Cervical Cancer Patients

Wang

Schmoeckel

Kost

et al. 2019

Cancers

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“…In vitro putrescine (polyamine) secreted by TAMs significantly attenuated 5-FU-induced growth inhibition of SW-480 and HCT-116 cell lines (143). 5-FU treatment induces CCL22 secretion by M2 macrophages in vitro (144). Co-culture of colon cancer cells and M2 macrophages treated with 5-FU indicated that macrophages mediate cell migration and invasion in CRC cells inducing EMT and activating PI3K/AKT pathway (144).…”

Section: Tams and Colorectal Cancer Treatmentmentioning

confidence: 99%

“…5-FU treatment induces CCL22 secretion by M2 macrophages in vitro (144). Co-culture of colon cancer cells and M2 macrophages treated with 5-FU indicated that macrophages mediate cell migration and invasion in CRC cells inducing EMT and activating PI3K/AKT pathway (144). CCL22 neutralizing antibody increased the apoptosis in cancer cells.…”

Section: Tams and Colorectal Cancer Treatmentmentioning

confidence: 99%

Tumor-Associated Macrophages in Human Breast, Colorectal, Lung, Ovarian and Prostate Cancers

et al. 2020

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Tumor-associated macrophages (TAMs) are major innate immune cells that constitute up to 50% of the cell mass of human tumors. TAMs are highly heterogeneous cells that originate from resident tissue-specific macrophages and from newly recruited monocytes. TAMs' variability strongly depends on cancer type, stage, and intratumor heterogeneity. Majority of TAMs are programmed by tumor microenvironment to support primary tumor growth and metastatic spread. However, TAMs can also restrict tumor growth and metastasis. In this review, we summarized the knowledge about the role of TAMs in tumor growth, metastasis and in the response to cancer therapy in patients with five aggressive types of cancer: breast, colorectal, lung, ovarian, and prostate cancers that are frequently metastasize into distant organs resulting in high mortality of the patients. Two major TAM parameters are applied for the evaluation of TAM correlation with the cancer progression: total amount of TAMs and specific phenotype of TAMs identified by functional biomarkers. We summarized the data generated in the wide range of international patient cohorts on the correlation of TAMs with clinical and pathological parameters of tumor progression including lymphatic and hematogenous metastasis, recurrence, survival, therapy efficiency. We described currently available biomarkers for TAMs that can be measured in patients' samples (tumor tissue and blood). CD68 is the major biomarker for the quantification of total TAM amounts, while transmembrane receptors (stabilin-1, CD163, CD206, CD204, MARCO) and secreted chitinase-like proteins (YKL-39, YKL-40) are used as biomarkers for the functional TAM polarization. We also considered that specific role of TAMs in tumor progression can depend on the localization in the intratumoral compartments. We have made the conclusion for the role of TAMs in primary tumor growth, metastasis, and therapy sensitivity for breast, colorectal, lung, ovarian, and prostate cancers. In contrast to other cancer types, majority of clinical studies indicate that TAMs in colorectal cancer have protective role for the patient and interfere with primary tumor growth

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“…Through literature research, CCL22 was identi ed as up-stream regulator of PI3K/AKT pathway. Secreted by M2 macrophages, CCL22 regulates CRC cells' epithelial-mesenchymal transition (EMT), and promotes tumor's resistance to chemotherapy 29,30 . FLOT1 also induces EMT and alters cell cycle by modulating Erk/Akt signaling axis 31 .…”

Section: Discussionmentioning

confidence: 99%

Identification of an immune-related gene signature to improve prognosis prediction of colorectal cancer patients

Dai

Yao

et al. 2020

Preprint

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Background: Despite recent advance in immune therapy, great heterogeneity exists in colorectal cancer (CRC) patients’ outcome. In this study, we aimed to analyze the Immune-related gene (IRG) expression profiles from two independent public databases and develop an effective signature to forecast patients’ prognosis.Method: IRGs were collected from The Cancer Genome Atlas (TCGA) database to identify a prognostic genes signature, which was verified in Gene Expression Omnibus (GEO) database. Gene function enrichment and immune cell infiltration analyses were conducted. A prognostic nomogram was built incorporating the IRG signature with clinical risk factors.Results: The training and test datasets had 487 and 579 patients, respectively. A prognostic six-gene-signature (CCL22, LIMK1, MAPKAPK3, FLOT1, GPRC5B and IL20RB) was developed through feature selection, and yielded incredible differentiation between low and high-risk group in the training set (P < 0.001), which was confirmed in the test group (P < 0.001). The signature outperformed tumor staging regarding survival prediction. Go and KEGG functional annotation analysis suggested the signature were significantly enriched in metabolic process and regulation of immunity (P<0.05). When combined with clinical risk factors, the model showed robust prediction capability.Conclusion: The immune-related six-gene signature is a reliable prognostic indicator for CRC patients and could bring insight for personalized cancer management.

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<p>M2 macrophages confer resistance to 5-fluorouracil in colorectal cancer through the activation of CCL22/PI3K/AKT signaling</p>

Cited by 77 publications

References 39 publications

Higher CCL22+ Cell Infiltration is Associated with Poor Prognosis in Cervical Cancer Patients

Higher CCL22+ Cell Infiltration is Associated with Poor Prognosis in Cervical Cancer Patients

Tumor-Associated Macrophages in Human Breast, Colorectal, Lung, Ovarian and Prostate Cancers

Identification of an immune-related gene signature to improve prognosis prediction of colorectal cancer patients

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