The Effect of Intratumoral Interrelation among FOXP3+ Regulatory T cells on Treatment Response and Survival in Triple-Negative Breast Cancer

Goda, Noriko; Nakashima, Chika; Nagamine, Ichiro; Otagaki, Sunao

doi:10.20944/preprints202203.0297.v1

2022

DOI: 10.20944/preprints202203.0297.v1

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The Effect of Intratumoral Interrelation among FOXP3+ Regulatory T cells on Treatment Response and Survival in Triple-Negative Breast Cancer

Noriko Goda¹,

Chika Nakashima²,

Ichiro Nagamine³

et al.

Abstract: Triple-negative breast cancer (TNBC) is characterized by an active immune response. We evalu-ated intratumoral interrelation between FOXP3+ tumor-infiltrating lymphocytes and other cy-tokines in TNBC. Network analysis refined cytokines significantly correlate with FOPX3 in TNBC. Treatment response and prognosis imformation of patients and survival data from the TGCA and METABRIC databases were analyzed according to refined cytokines. Interleukin (IL)-33 was sig-nificantly expressed by TNBC cell lines than lumi… Show more

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Cited by 3 publications

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Predictive Roles of Baseline Stromal Tumor-Infiltrating Lymphocytes and Ki-67 in Pathologic Complete Response in an Early-Stage Triple-Negative Breast Cancer Prospective Trial

Abuhadra,

Sun,

Yam

et al. 2023

Cancers

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High stromal tumor-infiltrating lymphocytes (sTILs) are associated with improved pathologic complete response (pCR) in triple-negative breast cancer (TNBC). We hypothesize that integrating high sTILs and additional clinicopathologic features associated with pCR could enhance our ability to predict the group of patients on whom treatment de-escalation strategies could be tested. In this prospective early-stage TNBC neoadjuvant chemotherapy study, pretreatment biopsies from 408 patients were evaluated for their clinical and demographic features, as well as biomarkers including sTILs, Ki-67, PD-L1 and androgen receptor. Multivariate logistic regression models were developed to generate a computed response score to predict pCR. The pCR rate for the entire cohort was 41%. Recursive partitioning analysis identified ≥20% as the optimal cutoff for sTILs to denote 35% (143/408) of patients as having high sTILs, with a pCR rate of 59%, and 65% (265/408) of patients as having low sTILs, with a pCR rate of 31%. High Ki-67 (cutoff > 35%) was identified as the only predictor of pCR in addition to sTILs in the training set. This finding was verified in the testing set, where the highest computed response score encompassing both high sTILa and high Ki-67 predicted a pCR rate of 65%. Integrating Ki67 and sTIL may refine the selection of early stage TNBC patients for neoadjuvant clinical trials evaluating de-escalation strategies.

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Predictive Roles of Baseline Stromal Tumor-Infiltrating Lymphocytes and Ki-67 in Pathologic Complete Response in an Early-Stage Triple-Negative Breast Cancer Prospective Trial

Abuhadra,

Sun,

Yam

et al. 2023

Cancers

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show abstract

Triple-Negative Breast Cancer and Predictive Markers of Response to Neoadjuvant Chemotherapy: A Systematic Review

Ende

Nguyen

Jager

et al. 2023

IJMS

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Around 40–50% of all triple-negative breast cancer (TNBC) patients achieve a pathological complete response (pCR) after treatment with neoadjuvant chemotherapy (NAC). The identification of biomarkers predicting the response to NAC could be helpful for personalized treatment. This systematic review provides an overview of putative biomarkers at baseline that are predictive for a pCR following NAC. Embase, Medline and Web of Science were searched for articles published between January 2010 and August 2022. The articles had to meet the following criteria: patients with primary invasive TNBC without distant metastases and patients must have received NAC. In total, 2045 articles were screened by two reviewers resulting in the inclusion of 92 articles. Overall, the most frequently reported biomarkers associated with a pCR were a high expression of Ki-67, an expression of PD-L1 and the abundance of tumor-infiltrating lymphocytes, particularly CD8+ T cells, and corresponding immune gene signatures. In addition, our review reveals proteomic, genomic and transcriptomic markers that relate to cancer cells, the tumor microenvironment and the peripheral blood, which also affect chemo-sensitivity. We conclude that a prediction model based on a combination of tumor and immune markers is likely to better stratify TNBC patients with respect to NAC response.

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Decoding the IL-33/ST2 Axis: Its Impact on the Immune Landscape of Breast Cancer

Stojanovic,

Gajovic,

Jurisevic

et al. 2023

IJMS

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Interleukin-33 (IL-33) has emerged as a critical cytokine in the regulation of the immune system, showing a pivotal role in the pathogenesis of various diseases including cancer. This review emphasizes the role of the IL-33/ST2 axis in breast cancer biology, its contribution to cancer progression and metastasis, its influence on the tumor microenvironment and cancer metabolism, and its potential as a therapeutic target. The IL-33/ST2 axis has been shown to have extensive pro-tumorigenic features in breast cancer, starting from tumor tissue proliferation and differentiation to modulating both cancer cells and anti-tumor immune response. It has also been linked to the resistance of cancer cells to conventional therapeutics. However, the role of IL-33 in cancer therapy remains controversial due to the conflicting effects of IL-33 in tumorigenesis and anti-tumor response. The possibility of targeting the IL-33/ST2 axis in tumor immunotherapy, or as an adjuvant in immune checkpoint blockade therapy, is discussed.

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The Effect of Intratumoral Interrelation among FOXP3+ Regulatory T cells on Treatment Response and Survival in Triple-Negative Breast Cancer

Cited by 3 publications

References 40 publications

Predictive Roles of Baseline Stromal Tumor-Infiltrating Lymphocytes and Ki-67 in Pathologic Complete Response in an Early-Stage Triple-Negative Breast Cancer Prospective Trial

Predictive Roles of Baseline Stromal Tumor-Infiltrating Lymphocytes and Ki-67 in Pathologic Complete Response in an Early-Stage Triple-Negative Breast Cancer Prospective Trial

Triple-Negative Breast Cancer and Predictive Markers of Response to Neoadjuvant Chemotherapy: A Systematic Review

Decoding the IL-33/ST2 Axis: Its Impact on the Immune Landscape of Breast Cancer

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