Activin A Sustains the Metastatic Phenotype of Tumor-Associated Macrophages and Is a Prognostic Marker in Human Cutaneous Melanoma

Abstract Background: Interleukin-10 receptor B (IL10RB) is a subunit of the interleukin-10 receptor. As an important part of the interleukin-10 signaling pathway, IL10RB plays an essential role in the regulation of the immune response. However, studies of IL10RB in glioma are rare. The present study aimed to investigate the potential role of IL10RB in glioma.Methods: 611 glioma samples in TCGA dataset and 310 glioma samples in CGGA dataset were download and organized, then analyzed the clinical expression characteristics and prognostic value of IL10RB as well as its correlation with immune cell infiltration in these samples using R. Results: IL10RB expression was significantly higher in the glioma tissues than in the normal tissues and increased in gliomas, especially with malignant phenotype. The Kaplan-Meier survival analysis and Cox regression analysis indicated that IL10RB was significantly associated with poor prognosis in patients with glioma and could be used as an independent prognostic marker. Further functional analysis suggested that IL10RB was involved in immune responses, and high expression of IL10RB in the glioma tissue resulted in more infiltrated immune cells, especially macrophages. Moreover, IL10RB was found to be strongly correlated with marker genes of tumor-associated macrophages (TAMs) and M2 macrophages, but low or even no correlation with marker genes of M1 macrophages. In addition, there was also a significant association between IL10RB and immune checkpoints that suppress effective antitumor immune responses.Conclusions: Our results demonstrated that high expressed IL10RB was associated with the malignant progression of gliomas and poor prognosis, and it might be involved in the polarization of macrophages which play a crucial role in the immunosuppressive response of gliomas.

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MAFB is a biomarker for cancer severity and prognosis, and is a potential cancer immunotherapy target

10.21203/rs.3.rs-763431/v2 ◽

2021 ◽

Author(s):

Omar Samir ◽

Naohiro Kobayashi ◽

Mennatullah Siyam ◽

Manoj Yadav ◽

Yuri Inoue ◽

...

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Lung Adenocarcinoma ◽

Cancer Immunotherapy ◽

Prognostic Marker ◽

Tumor Associated Macrophages ◽

Poor Overall Survival ◽

Potential Target ◽

Pancreatic Cancers

Abstract MAFB is a transcription factor specifically expressed in macrophages. Tumor associated macrophages (TAMs) play a key role in the tumor microenvironment (TME) by inducing immunosuppression, angiogenesis, tumor invasion, and metastasis. However, finding a suitable specific biomarker and target for TAMs is challenging. Our previous study1 suggested that MAFB could be a suitable marker for tumor-associated macrophages (TAMs) besides MAFB is expressed in anti-inflammatory alternatively activated M2 macrophages in vitro. In the current study, in a cohort of patients with lung adenocarcinoma (n = 120), increased MAFB expression was related to increased metastasis and poor overall survival rate. Our findings indicate that MAFB can be used as a prognostic marker for assessing metastatic potential in patients with lung adenocarcinoma. Further, we showed that MAFB expression was positively correlated with the expression of CD204 and CD68 in hepatocarcinoma, colon and pancreatic cancers. We demonstrated that MAFB could be used as a biomarker for TAMs and consequently, for assessing severity in various human cancers, including lung, liver, colon, and pancreatic cancers, according to the immunohistochemical analysis of the expression of MAFB, CD68, and CD204. In addition, we showed that MAFB was expressed in TAMs expressing Programmed cell death protein-1 and/or Programmed cell death ligand 1 (TAM PD-1+ and TAM PD-L1+) cells in lung adenocarcinoma and Lewis lung carcinoma (LLC) mouse model. These findings indicate that MAFB can be a potential target for drug development against TAM PD-1+ and TAM PD-L1+ cells. In summary, transcriptional factor MAFB can be used as a specific biomarker, prognostic marker, and a potential target for cancer immunotherapy against TAMs.

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KIT mutational status does not constitute an independent prognostic marker in cutaneous melanoma. A study on 688 Spanish patients

Melanoma Research ◽

10.1097/cmr.0000000000000712 ◽

2021 ◽

Vol 31 (1) ◽

pp. 101-103

Author(s):

David Millán-Esteban ◽

Zaida García-Casado ◽

Esperanza Manrique-Silva ◽

Rajiv Kumar ◽

Eduardo Nagore

Keyword(s):

Prognostic Marker ◽

Cutaneous Melanoma ◽

Independent Prognostic Marker ◽

Mutational Status

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MAFB is a biomarker for cancer severity, prognostic marker, and a potential target for cancer immunotherapy

10.21203/rs.3.rs-763431/v1 ◽

2021 ◽

Author(s):

Samir Omar ◽

Naohiro Kobayashi ◽

Mennatullah Siyam ◽

Manoj Yadav ◽

Yuri Inoue ◽

...

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Cancer Immunotherapy ◽

Prognostic Marker ◽

Mouse Tumor ◽

Tumor Associated Macrophages ◽

Potential Target ◽

Pancreatic Cancers ◽

Lung Adenocarcinomas

Abstract MAFB is a transcription factor specifically expressed in macrophages. Using in vitro and in vivo in mouse tumor models, our previous study suggested that MAFB could be a suitable marker for tumor-associated macrophages (TAMs), besides MAFB is expressed in anti-inflammatory alternatively activated M2 macrophages in vitro. TAMs play a key role in the tumor microenvironment (TME) by inducing immunosuppression, angiogenesis, tumor invasion, and metastasis. However, finding a suitable specific biomarker and target for TAMs is challenging. Here, we demonstrated that MAFB could be used as a biomarker for TAMs and consequently, for severity in various human cancers, including lung, liver, colon, and pancreatic cancers, according to the immunohistochemical analysis of the expression of MAFB, CD68, and CD204. Moreover, In a cohort of lung adenocarcinomas patients (n = 120), increased MAFB expression was related to increased tendency towards metastasis and poor overall survival rate. Further, we showed that MAFB expression was positively correlated to the expression of CD204 and CD68 in both human hepatocarcinoma and colon cancers. Our findings indicate that MAFB as a specific biomarker can be used as prognostic marker for Metastasis potential in Lung adenocarcinomas patients and also a biomarker for the severe Liver, Colon and pancreatic cancers. In addition, we showed that MAFB was expressed in Tumor associated macrophages expressing Programmed cell death protein-1 and/or Programmed cell death ligand 1 (TAM PD-1+ and TAM PD-L1+) cells in both human lung adenocarcinomas and Lewis lung carcinoma (LLC) mouse model. These findings indicate that MAFB can be a potential target for drug development against TAM PD-1+ and TAM PD-L1+ cells. In summary, transcriptional factor MAFB can be used as a specific biomarker, prognostic marker and a potential target for cancer immunotherapy against TAMs.

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Abstract 3927: The presence of COX-2 and tumor-associated macrophages as a prognostic marker for invasive breast carcinoma patients

10.1158/1538-7445.am2016-3927 ◽

2016 ◽

Author(s):

Karla Esbona ◽

Sandeep Saha ◽

Yanyao Yi ◽

Menggang Yu ◽

Kari Wisinski ◽

...

Keyword(s):

Breast Carcinoma ◽

Prognostic Marker ◽

Invasive Breast Carcinoma ◽

Tumor Associated Macrophages ◽

Cox 2

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Serum S-100 protein: a potentially useful prognostic marker in cutaneous melanoma

British Journal of Dermatology ◽

10.1046/j.1365-2133.1997.18531946.x ◽

1997 ◽

Vol 137 (3) ◽

pp. 381-385 ◽

Cited By ~ 1

Author(s):

H.D. ABRAHA ◽

L.C. FULLER ◽

A.W.P. DU VIVIER ◽

E.M. HIGGINS ◽

R.A. SHERWOOD

Keyword(s):

Prognostic Marker ◽

Cutaneous Melanoma ◽

Protein A ◽

S 100

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Melanoma-Derived Exosomal miR-125b-5p Educates Tumor Associated Macrophages (TAMs) by Targeting Lysosomal Acid Lipase A (LIPA)

Cancers ◽

10.3390/cancers12020464 ◽

2020 ◽

Vol 12 (2) ◽

pp. 464 ◽

Cited By ~ 12

Author(s):

Dennis Gerloff ◽

Jana Lützkendorf ◽

Rose K.C. Moritz ◽

Tom Wersig ◽

Karsten Mäder ◽

...

Keyword(s):

Immune Cells ◽

Cutaneous Melanoma ◽

Acid Lipase ◽

Tumor Associated Macrophages ◽

Lysosomal Acid ◽

Lysosomal Acid Lipase ◽

Phenotype Switch ◽

Lipase A ◽

Underlying Mechanisms ◽

First Time

Tumor-associated macrophages (TAMs) are the most abundant immune cells in the tumor microenvironment, promoting tumor initiation, growth, progression, metastasis, and immune evasion. Recently it was shown that cancer cell-derived exosomes induce a tumor-promoting phenotype in TAMs. Exosome-loaded proteins, DNA, and RNAs may contribute to the macrophage reprogramming. However, the exact mediators and mechanisms, particularly in melanoma, are not known. In this study we examined the effects of cutaneous melanoma-derived exosomes on macrophage function and the underlying mechanisms. First, we showed that exposure to melanoma exosomes induces a tumor-promoting TAM phenotype in macrophages. Sequencing revealed enrichment for several miRNAs including miR-125b-5p in cutaneous melanoma exosomes. We showed that miR-125b-5p is delivered to macrophages by melanoma exosomes and partially induces the observed tumor-promoting TAM phenotype. Finally, we showed that miR-125b-5p targets the lysosomal acid lipase A (LIPA) in macrophages, which in turn contributes to their phenotype switch and promotes macrophage survival. Thus, our data show for the first time that miR-125b-5p transferred by cutaneous melanoma-derived exosomes induces a tumor-promoting TAM phenotype in macrophages.

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