FOXP3 in Melanoma with Regression: Between Tumoral Expression and Regulatory T Cell Upregulation

Cioplea, Mirela; Nichita, Luciana; Georgescu, Dan; Sticlaru, Liana; Cioroianu, Alexandra; Nedelcu, Roxana Ioana; Turcu, Gabriela; Rauta, Alin; Mogodici, Cristian; Zurac, Sabina; Popp, Cristiana

doi:10.1155/2020/5416843

Cited by 7 publications

(8 citation statements)

References 29 publications

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“…Regarding the TILs, increased infiltration of FoxP3+ Tregs was associated with improved OS in colorectal, head and neck, and esophageal cancer, whereas in melanoma, lung, cervical, renal, hepatocellular, gastric, and breast cancers, it was linked with shorter OS [ 27 ]. On the other hand, while the higher count of FoxP3-positive tumor cells predicts better survival in gastric and prostate cancers [ 24 , 28 , 29 ], in melanoma and NSCLC, high expression was associated with an unfavorable clinical prognosis, leading to shorter overall survival and recurrence-free survival [ 30 , 31 ]. However, none of these studies analyzed the prognostic value of FoxP3 specifically in patients treated with ICI.…”

Section: Discussionmentioning

confidence: 99%

FoxP3 Expression in Tumor-Infiltrating Lymphocytes as Potential Predictor of Response to Immune Checkpoint Inhibitors in Patients with Advanced Melanoma and Non-Small Cell Lung Cancer

Grell

Borilova

Fabián

et al. 2023

Cancers

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Immune checkpoint inhibitors (ICI) are the main therapy currently used in advanced malignant melanoma (MM) and non-small cell lung cancer (NSCLC). Despite the wide variety of uses, the possibility of predicting ICI efficacy in these tumor types is scarce. The aim of our study was to find new predictive biomarkers for ICI treatment. We analyzed, by immunohistochemistry, various cell subsets, including CD3+, CD8+, CD68+, CD20+, and FoxP3+ cells, and molecules such as LAG-3, IDO1, and TGFβ. Comprehensive genomic profiles were analyzed. We evaluated 46 patients with advanced MM (31) and NSCLC (15) treated with ICI monotherapy. When analyzing the malignant melanoma group, shorter median progression-free survival (PFS) was found in tumors positive for nuclear FoxP3 in tumor-infiltrating lymphocytes (TILs) (p = 0.048, HR 3.04) and for CD68 expression (p = 0.034, HR 3.2). Longer PFS was achieved in patients with tumors with PD-L1 TPS ≥ 1 (p = 0.005, HR 0.26). In the NSCLC group, only FoxP3 positivity was associated with shorter PFS and OS. We found that FoxP3 negativity was linked with a better response to ICI in both histological groups.

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Section: Discussionmentioning

confidence: 99%

FoxP3 Expression in Tumor-Infiltrating Lymphocytes as Potential Predictor of Response to Immune Checkpoint Inhibitors in Patients with Advanced Melanoma and Non-Small Cell Lung Cancer

Grell

Borilova

Fabián

et al. 2023

Cancers

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“…We used the digital approach to identify cytokeratin + and FOXP3 + tumor cells. The expression of FOXP3 in tumor cells has been linked to poor prognosis in several cancers, 17,22 and as far as we know, expression of FOXP3 in prostate tumor cells has not yet been investigated. We identified tumor cells with FOXP3 expression, but could not verify any difference in tumor cell FOXP3 expression between treatments.…”

Section: Discussionmentioning

confidence: 99%

Infiltrating immune cells in prostate cancer tissue after androgen deprivation and radiotherapy

Erlandsson

Lundholm

Watz

et al. 2023

Int J Immunopathol Pharmacol

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Objectives Androgen deprivation therapy (ADT) has long been a cornerstone in treatment of advanced prostate cancer (PCa), and is known to improve the results of radiotherapy (RT) for high-risk disease. The purpose of our study was to use a multiplexed immunohistochemical (mIHC) approach to investigate the infiltration of immune cells in PCa tissue after eight weeks of ADT and/or RT with 10 Gy. Methods From a cohort of 48 patients divided into two treatment arms, we obtained biopsies before and after treatment and used a mIHC method with multispectral imaging to analyze the infiltration of immune cells in tumor stroma and tumor epithelium, focusing on areas with high infiltration. Results Tumor stroma showed a significantly higher infiltration of immune cells compared to tumor epithelium. The most prominent immune cells were CD20+ B-lymphocytes, followed by CD68+ macrophages, CD8+ cytotoxic T-cells, FOXP3+ regulatory T-cells (Tregs), and T-bet+ Th1-cells. Neoadjuvant ADT followed by RT significantly increased the infiltration of all five immune cells. Numbers of Th1-cells and Tregs significantly increased after single treatment with ADT or RT. In addition, ADT alone increased the number of cytotoxic T-cells and RT increased the number of B-cells. Conclusions Neoadjuvant ADT in combination with RT results in a higher inflammatory response compared to RT or ADT alone. The mIHC method may be a useful tool for investigating infiltrating immune cells in PCa biopsies to understand how immunotherapeutic approaches can be combined with current PCa therapies.

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“…However, excessive work in the TME helps tumor progression. Many effector Tregs with strong inhibitory activity infiltrate the local tumor area in various cancer types, such as melanoma, and suppress the antitumor immune response [ 114 ]. Tregs are mobilized by regulating the CCL6/CCL20 axis and are activated by TCR engagement with IL-10 and TGF-β signaling [ 115 ].…”

Section: Immune Network In Hcc Microenvironmentmentioning

confidence: 99%

Tumor Immune Microenvironment and Immunosuppressive Therapy in Hepatocellular Carcinoma: A Review

Oura

Morishita

Tani

et al. 2021

IJMS

266

180

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Liver cancer has the fourth highest mortality rate of all cancers worldwide, with hepatocellular carcinoma (HCC) being the most prevalent subtype. Despite great advances in systemic therapy, such as molecular-targeted agents, HCC has one of the worst prognoses due to drug resistance and frequent recurrence and metastasis. Recently, new therapeutic strategies such as cancer immunosuppressive therapy have prolonged patients’ lives, and the combination of an immune checkpoint inhibitor (ICI) and VEGF inhibitor is now positioned as the first-line therapy for advanced HCC. Since the efficacy of ICIs depends on the tumor immune microenvironment, it is necessary to elucidate the immune environment of HCC to select appropriate ICIs. In this review, we summarize the findings on the immune microenvironment and immunosuppressive approaches focused on monoclonal antibodies against cytotoxic T lymphocyte-associated protein 4 and programmed cell death protein 1 for HCC. We also describe ongoing treatment modalities, including adoptive cell transfer-based therapies and future areas of exploration based on recent literature. The results of pre-clinical studies using immunological classification and animal models will contribute to the development of biomarkers that predict the efficacy of immunosuppressive therapy and aid in the selection of appropriate strategies for HCC treatment.

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FOXP3 in Melanoma with Regression: Between Tumoral Expression and Regulatory T Cell Upregulation

Cited by 7 publications

References 29 publications

FoxP3 Expression in Tumor-Infiltrating Lymphocytes as Potential Predictor of Response to Immune Checkpoint Inhibitors in Patients with Advanced Melanoma and Non-Small Cell Lung Cancer

FoxP3 Expression in Tumor-Infiltrating Lymphocytes as Potential Predictor of Response to Immune Checkpoint Inhibitors in Patients with Advanced Melanoma and Non-Small Cell Lung Cancer

Infiltrating immune cells in prostate cancer tissue after androgen deprivation and radiotherapy

Tumor Immune Microenvironment and Immunosuppressive Therapy in Hepatocellular Carcinoma: A Review

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