FOXP3/HAT1 Axis Controls Treg Infiltration in the Tumor Microenvironment by Inducing CCR4 Expression in Breast Cancer

Sarkar, Tania; Dhar, Subhanki; Chakraborty, Debasis; Pati, Subhadip; Bose, Sugata; Panda, Abir K.; Basak, Udit; Chakraborty, Sourio; Mukherjee, Sumon; Guin, Aharna; Jana, Kuladip; Sarkar, Diptendra Kumar; Sa, Gaurisankar

doi:10.3389/fimmu.2022.740588

Cited by 30 publications

(25 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been shown that inhibition of CCR4 signaling diminishes Treg infiltration of the TME while Treg numbers are maintained in the periphery (54). Furthermore, depleting CCR4 + Tregs seems to reduce the tumor burden both as a standalone therapy and in combination with checkpoint blockade in certain tumor settings (54,(56)(57)(58)(59)(60). Despite the potential of targeting CCR4 for immunotherapies, exact role of CCR4 in Treg development, function and tumor-Treg crosstalk remains elusive (61).…”

Section: Migration and Homing Of Tregs To Tumor Sitementioning

confidence: 99%

Exhaust the exhausters: Targeting regulatory T cells in the tumor microenvironment

McRitchie

Akkaya²

2022

Front. Immunol.

View full text Add to dashboard Cite

The concept of cancer immunotherapy has gained immense momentum over the recent years. The advancements in checkpoint blockade have led to a notable progress in treating a plethora of cancer types. However, these approaches also appear to have stalled due to factors such as individuals’ genetic make-up, resistant tumor sub-types and immune related adverse events (irAE). While the major focus of immunotherapies has largely been alleviating the cell-intrinsic defects of CD8+ T cells in the tumor microenvironment (TME), amending the relationship between tumor specific CD4+ T cells and CD8+ T cells has started driving attention as well. A major roadblock to improve the cross-talk between CD4+ T cells and CD8+ T cells is the immune suppressive action of tumor infiltrating T regulatory (Treg) cells. Despite their indispensable in protecting tissues against autoimmune threats, Tregs have also been under scrutiny for helping tumors thrive. This review addresses how Tregs establish themselves at the TME and suppress anti-tumor immunity. Particularly, we delve into factors that promote Treg migration into tumor tissue and discuss the unique cellular and humoral composition of TME that aids survival, differentiation and function of intratumoral Tregs. Furthermore, we summarize the potential suppression mechanisms used by intratumoral Tregs and discuss ways to target those to ultimately guide new immunotherapies.

show abstract

Section: Migration and Homing Of Tregs To Tumor Sitementioning

confidence: 99%

Exhaust the exhausters: Targeting regulatory T cells in the tumor microenvironment

McRitchie

Akkaya²

2022

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…Tumor-in ltrating Tregs express higher chemokine receptor CCR4 than peripheral Tregs in BRCA patients according to studies. At the same time, FoxP3, as a CCR4 transcription activator , can increase CCR4 expression in Tregs and promote of BRCA immune escape [37]. In addition, Tregs can reduce CD80/CD86 expression of APCs via CTLA-4dependent autophagy, thereby inhibiting the T-cell stimulating activity of APCs.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of prognosis and immune function of CD70-CD27 signaling axis in pan-cancer

Kong

Xiong

2023

Funct Integr Genomics

View full text Add to dashboard Cite

The immune checkpoint molecule CD70 and its receptor CD27 constitute the signal transduction axis, which is abnormally expressed in many solid tumors and is crucial for T cell co-stimulation and immune escape. Tumor cells regulate the expression of CD27 by expressing CD70 in tumor microenvironment and promote immune escape.The discovery of the immunosuppressive effect of the CD70-CD27 signaling axis on tumor cells introduces a new anti-tumor immunotherapy -CD70. Although current research evidence suggests a link between CD70 and tumors, no pan-cancer analysis is available. Using the Cancer Genome Atlas and Gene Expression Omnibus datasets, we rst explored the potential carcinogenic role of the CD70-CD27 signaling axis in human malignancies. CD70 expression is up-regulated in most cancers and has an obvious correlation with the prognosis of tumor patients. The expression of CD70 and CD27 is associated with the level of regulatory T cells (Tregs) in ltration. In addition, T cell receptor signaling pathways, PI3K-Akt, NF-κB, and TNF signaling pathways are also involved in CD70-mediated immune escape. CD70 mainly regulates tumor immune escape by regulating T cell-mediated tumor killing, while Tregs may be its main T cell subset. Our rst pan-cancer study provides a relatively comprehensive understanding of the carcinogenic role of the CD70-CD27 signaling axis in different tumors.

show abstract

“…It can be assumed that infiltration of CCL20 into the TME from the blood compartment could play a vital role in tumor eradication, thereby affecting the prognosis. CCL17 is known to be released by tumor cells and tumor-associated macrophages, and promotes tumor development [ 19 ]. However, levels of CCL17 may represent a marker of interest to study in HNC, as increased serum levels have been shown to be associated with longer survival in melanoma patients with metastasis [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Serum Proteomics in Patients with Head and Neck Cancer: Peripheral Blood Immune Response to Treatment

Astradsson

Sellberg

Ehrsson

et al. 2022

IJMS

View full text Add to dashboard Cite

In this real-world study, the aims were to prospectively evaluate the expression of inflammatory proteins in serum collected from head and neck cancer patients before and after treatment, and to assess whether there were differences in expression associated with treatment modalities. The mixed study cohort consisted of 180 patients with head and neck cancer. The most common tumor sites were the oropharynx (n = 81), the oral cavity (n = 53), and the larynx (n = 22). Blood tests for proteomics analysis were carried out before treatment, 7 weeks after the start of treatment, and 3 and 12 months after the termination of treatment. Sera were analyzed for 83 proteins using an immuno-oncology biomarker panel (Olink, Uppsala, Sweden). Patients were divided into four treatment groups: surgery alone (Surg group, n = 24), radiotherapy with or without surgery (RT group, n = 94), radiotherapy with concomitant cisplatin (CRT group, n = 47), and radiotherapy with concomitant targeted therapy (RT Cetux group, n = 15). For the overall cohort, the expression levels of 15 of the 83 proteins changed significantly between the pretreatment sample and the sample taken 7 weeks after the start of treatment. At 7 weeks after the start of treatment, 13 proteins showed lower expression in the CRT group compared to the RT group. The majority of the inflammatory proteins had returned to their pretreatment levels after 12 months. It was clearly demonstrated that cisplatin-based chemoradiation has immunological effects in patients with head and neck cancer. This analysis draws attention to several inflammatory proteins that are of interest for further studies.

show abstract

FOXP3/HAT1 Axis Controls Treg Infiltration in the Tumor Microenvironment by Inducing CCR4 Expression in Breast Cancer

Cited by 30 publications

References 53 publications

Exhaust the exhausters: Targeting regulatory T cells in the tumor microenvironment

Exhaust the exhausters: Targeting regulatory T cells in the tumor microenvironment

Comprehensive analysis of prognosis and immune function of CD70-CD27 signaling axis in pan-cancer

Serum Proteomics in Patients with Head and Neck Cancer: Peripheral Blood Immune Response to Treatment

Contact Info

Product

Resources

About