TGF-β and Cancer Immunotherapy

Maruyama, Takashi; Chen, Wanjun; Shibata, Hiroyuki

doi:10.1248/bpb.b21-00966

Cited by 35 publications

(48 citation statements)

References 82 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…B cell receptor richness in low-risk patients was also increased (Figure 6C), while the BCR diversity was comparable (Figure 6D). IFN-γ is a pleiotropic cytokine with antitumor or pro-tumorigenic roles 36 , and TGF-β is an important cancer-promoting cytokine that contributes to the suppression of anti-tumor immunity 37 (TGF-β and Cancer Immunotherapy). We subsequently scored the IFN-γ and TGF-β responses and found that both cytokine responses were enhanced in high-risk patients (Figure 6E-F).…”

Section: The Signature Correlates With Anti-tumor Immunity and Therap...mentioning

confidence: 99%

A Novel Fatty Acid Metabolism Signature Predicts Prognoses, Tumor Immune Microenvironment, and Immunotherapy Response In Lung Adenocarcinoma

Zhang

Fan

et al. 2023

Preprint

View full text Add to dashboard Cite

Background: Lung adenocarcinoma (LUAD) is the most common and aggressive subtype of non-small cell lung cancer. Aberrant fatty acid metabolism (FAM) has been demonstrated to play an essential role in the tumorigenesis of human cancers, yet limited studies in LUAD. Methods: The RNA-sequencing dataset of LUAD patients with clinical features from the TCGA database was used as the training set. Six independent LUAD cohorts totaling 1,368 encompassing diverse platforms from the GEO database were employed as validation sets. The prognostic signature was constructed by multivariate Cox regression analysis with the Akaike information criterion. The tumor immune microenvironment (TIME) was analyzed by ESTIMATE and infiltrated immune cell subsets were calculated using multiple deconvolution algorithms. Tumor characteristics such as T cell receptors richness and diversity, and tumor mutation burden (TMB) were assessed. The implication of the signature in predicting immunotherapy response was also investigated. Results: Overall survival (OS) related FAMGs were identified. A robust prognostic signature for OS prediction was developed. Patients were divided into high- and low-risk groups and decreased OS was observed in low-risk patients. Furthermore, the signature could be an independent prognostic indicator after adjusting for clinicopathological features. Receiver operating characteristic curve analysis indicated the validity of the signature. The predictive power was validated using six LUAD validation cohorts. The signature also has strong risk stratification utility for patients’ disease relapse. TIME analysis showed increased immune activity in low-risk patients, which was convinced by higher infiltrated CD8+ T, natural killer, and B cells, as well as lower tumor purity, stemness index, TMB, and cell proliferation. Additionally, elevated activated and less senescence of immune cells were observed in low-risk patients. Differentially expressed pathways that related to resistance to immune checkpoint blockades such as DNA repair, hypoxia, cell cycle, epithelial-mesenchymal-transition, and oxidative phosphorylation were enriched in high-risk patients. T cell receptor richness and diversity were higher in low-risk patients. Responders had lower risk scores in contrast to non-responders for LUAD patients receiving anti-PD-1 treatment. Conclusions: The study was the first time to establish a novel FAMGs-based signature in recognition of the prognosis for LUAD patients and evaluation of the possibility of immunotherapy response in personalized treatment.

show abstract

Section: The Signature Correlates With Anti-tumor Immunity and Therap...mentioning

confidence: 99%

A Novel Fatty Acid Metabolism Signature Predicts Prognoses, Tumor Immune Microenvironment, and Immunotherapy Response In Lung Adenocarcinoma

Zhang

Fan

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Given that TGFβ protects tumour cells from the immune system and cancer cells stimulate immune checkpoint inhibitory receptors, anti-tumourigenic immunotherapies are being developed to stimulate immune-mediated destruction of tumour cells ( Bai et al, 2019 ). As such, numerous clinical trials are assessing the efficacy of combining immune checkpoint inhibitors alongside TGFβ signalling antagonists ( Maruyama et al, 2022 ). For instance, ABBV-151 and Budigalimab (formerly known as ABBV-181), anti-TGFβ1 and anti-programmed cell death receptor one antibodies, respectively, have begun phase I clinical trials for advanced solid tumours ( Powderly et al, 2020 ).…”

Section: Targeting Tgfβ Signalling In Cancer Therapymentioning

confidence: 99%

Transforming growth factor-β in tumour development

Trelford

Dagnino

Guglielmo

2022

Front. Mol. Biosci.

View full text Add to dashboard Cite

Transforming growth factor-β (TGFβ) is a ubiquitous cytokine essential for embryonic development and postnatal tissue homeostasis. TGFβ signalling regulates several biological processes including cell growth, proliferation, apoptosis, immune function, and tissue repair following injury. Aberrant TGFβ signalling has been implicated in tumour progression and metastasis. Tumour cells, in conjunction with their microenvironment, may augment tumourigenesis using TGFβ to induce epithelial-mesenchymal transition, angiogenesis, lymphangiogenesis, immune suppression, and autophagy. Therapies that target TGFβ synthesis, TGFβ-TGFβ receptor complexes or TGFβ receptor kinase activity have proven successful in tissue culture and in animal models, yet, due to limited understanding of TGFβ biology, the outcomes of clinical trials are poor. Here, we review TGFβ signalling pathways, the biology of TGFβ during tumourigenesis, and how protein quality control pathways contribute to the tumour-promoting outcomes of TGFβ signalling.

show abstract

“…IL-10 upregulates the expression of glycosyltransferase, Mgat5 in CD8 + T-cells to induce the N-glycan branching of TCR that restricts the association of co-receptor CD8 with TCR. This event ultimately hampers the TCR signaling, and antigen sensitivity IL-10 also supports the growth of M2 macrophages and suppresses the M1 polarization [ 111 , 112 , 113 ]. TAM-secreted TGF-β1 downregulates the MiR-34a expression to stimulate the proliferation and invasion of colorectal cancer cells by upregulating the vascular endothelial growth factor [ 40 ].…”

Section: Pro-tumorigenic Roles Of Tamsmentioning

confidence: 99%

Macrophages as a Potential Immunotherapeutic Target in Solid Cancers

et al. 2022

View full text Add to dashboard Cite

The revolution in cancer immunotherapy over the last few decades has resulted in a paradigm shift in the clinical care of cancer. Most of the cancer immunotherapeutic regimens approved so far have relied on modulating the adaptive immune system. In recent years, strategies and approaches targeting the components of innate immunity have become widely recognized for their efficacy in targeting solid cancers. Macrophages are effector cells of the innate immune system, which can play a crucial role in the generation of anti-tumor immunity through their ability to phagocytose cancer cells and present tumor antigens to the cells of adaptive immunity. However, the macrophages that are recruited to the tumor microenvironment predominantly play pro-tumorigenic roles. Several strategies targeting pro-tumorigenic functions and harnessing the anti-tumorigenic properties of macrophages have shown promising results in preclinical studies, and a few of them have also advanced to clinical trials. In this review, we present a comprehensive overview of the pathobiology of TAMs and their role in the progression of solid malignancies. We discuss various mechanisms through which TAMs promote tumor progression, such as inflammation, genomic instability, tumor growth, cancer stem cell formation, angiogenesis, EMT and metastasis, tissue remodeling, and immunosuppression, etc. In addition, we also discuss potential therapeutic strategies for targeting TAMs and explore how macrophages can be used as a tool for next-generation immunotherapy for the treatment of solid malignancies.

show abstract

TGF-β and Cancer Immunotherapy

Cited by 35 publications

References 82 publications

A Novel Fatty Acid Metabolism Signature Predicts Prognoses, Tumor Immune Microenvironment, and Immunotherapy Response In Lung Adenocarcinoma

A Novel Fatty Acid Metabolism Signature Predicts Prognoses, Tumor Immune Microenvironment, and Immunotherapy Response In Lung Adenocarcinoma

Transforming growth factor-β in tumour development

Macrophages as a Potential Immunotherapeutic Target in Solid Cancers

Contact Info

Product

Resources

About