Targeting immune pathways in breast cancer: review of the prognostic utility of TILs in early stage triple negative breast cancer (TNBC)

Blackley, Elizabeth F.; Loi, Sherene

doi:10.1016/s0960-9776(19)31122-1

Cited by 52 publications

(39 citation statements)

References 19 publications

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“…Studies have proved that TIL levels have a strong prognostic value, which can improve the distant recurrence-free survival, disease-free, and overall survival estimates for TNBC patients treated with adjuvant/neoadjuvant chemotherapy (22,23). Increased TIL levels have been observed to be positively correlated with prolonged survival and increased pathological complete response rates (24)(25)(26).…”

Section: Discussionmentioning

confidence: 99%

Correlation Between Mammographic Radiomics Features and the Level of Tumor-Infiltrating Lymphocytes in Patients With Triple-Negative Breast Cancer

Meng

Huang

et al. 2020

Front. Oncol.

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Objectives: Tumor-infiltrating lymphocytes (TILs) have been identified as a significant prognostic indicator of response to neoadjuvant therapy and immunotherapy for triple-negative breast cancer (TNBC) patients. Herein, we aim to assess the association between TIL levels and mammographic features in TNBC patients. Methods: Forty-three patients with surgically proven TNBC who underwent preoperative mammography from January 2018 to December 2018 were recruited. Pyradiomics software was used to extract 204 quantitative radiomics features, including morphologic, grayscale, and textural features, from the segmented lesion areas. The correlation between radiological characteristics and TIL levels was evaluated by screening the most statistically significant radiological features using Mann-Whitney U-test and Pearson correlation coefficient. The patients were divided into two groups based on tumor TIL levels: patients with TIL levels <50% and those with TIL levels ≥50%. The correlation between TIL levels and clinicopathological characteristics was assessed using the chi-square test or Fisher's exact test. Mann-Whitney U-test and Pearson correlation coefficient were used to analyze the statistical significance and Pearson correlation coefficient of clinical pathological features, age, and radiological features. Conclusion: Mammography features not only distinguish high and low TIL levels in TNBC patients but also can act as imaging biomarkers to enhance diagnosis and the response of patients to neoadjuvant therapies and immunotherapies.

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Section: Discussionmentioning

confidence: 99%

Correlation Between Mammographic Radiomics Features and the Level of Tumor-Infiltrating Lymphocytes in Patients With Triple-Negative Breast Cancer

Meng

Huang

et al. 2020

Front. Oncol.

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“…CD4 + Th1 cells secrete IL-2 and IFN to activate and promote the proliferation of CD8 + T cells, which subsequently release cytotoxic cytokines and kill cancer cells directly [25]. Accumulating data prove that CD4 + Th1 cells and CD8 + T cells are associated with better survival both in the early stage and metastatic TNBC, which may serve as a promising marker for identifying patients who are more likely to bene t from ICIs [26][27][28][29]. As a typically pro-tumorigenic cell, M2 macrophage plays an immunosuppressive role in the TME by inhibiting the activation of M1 macrophage and secreting IL-10 and TGF-β [30].…”

Section: Discussionmentioning

confidence: 99%

A Risk Scoring System Based on Tumor Microenvironment Cells to Predict Prognosis and Immune Activity in Triple-Negative Breast Cancer

Yang

et al. 2021

Preprint

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The tumor microenvironment (TME) interacting with the malignant cells plays a vital role in cancer development. Herein, we aim to establish and verify a scoring system based on the characteristics of TME cells for prognosis prediction and personalized treatment guidance in patients with triple-negative breast cancer (TNBC). 158 TNBC samples from The Cancer Genome Atlas (TCGA) were included as the training cohort, and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) (N = 297), as well as GSE58812 (N = 107), were included as the validation cohort. The enrichment scores of 64 immune and stromal cells were estimated by the xCell algorithm. In the training cohort, cells with prognostic significance were found out using univariate Cox regression analysis and further applied to the random survival forest (RSF) model. Basing on the scores of M2 macrophages, CD8+ T cells, and CD4+ memory T cells, a risk scoring system was constructed, which divided TNBC patients into 4 phenotypes (M2low, M2highCD8+ThighCD4+Thigh, M2highCD8+ThighCD4+Tlow, and M2highCD8+Tlow) and 2 groups. The low-risk group had superior survival outcomes than the high-risk one, which was further confirmed in the validation cohort. Moreover, in the low-risk group, immune-related pathways were significantly enriched, and a higher level of antitumoral immune cells and immune checkpoint molecules, including PD-L1, PD-1, and CTLA-4, could be observed. Additionally, consistent results were achieved in the SYSUCC cohort when the scoring system was applied. In summary, this novel scoring system might predict the survival and immune activity of patients and might serve as a potential index for immunotherapy.

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“…Alternative therapies for TNBC are in great demand (40) and the impact of the TME on γδ T cells is of great interest to those wishing to further develop γδ T cell immunotherapy (31). For example, altered tumor cell metabolism was addressed in a recent study describing harmful effects of LDL cholesterol on Vδ2 γδ T cell cytokine production and cytotoxicity against MDA-MB-231 in vitro and in vivo, which may well occur in the TME (41).…”

Section: Discussionmentioning

confidence: 99%

Aberrantly Expressed Embryonic Protein NODAL Alters Breast Cancer Cell Susceptibility to γδ T Cell Cytotoxicity

et al. 2020

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Gamma delta (γδ) T cells kill transformed cells, and increased circulating γδ T cells levels correlate with improved outcome in cancer patients; however, their function within the breast tumor microenvironment (TME) remains controversial. As tumors progress, they begin to express stem-cell associated proteins, concomitant with the emergence of therapy resistant metastatic disease. For example, invasive breast cancers often secrete the embryonic morphogen, NODAL. NODAL has been shown to promote angiogenesis, therapy resistance and metastasis in breast cancers. However, to date, little is known about how this secreted protein may interact with cells in the TME. Herein we explore how NODAL in the TME may influence γδ T cell function. We have assessed the proximity of γδ T cells to NODAL in a cohort of triple negative breast tumors. In all cases in which γδ T cells could be identified in these tumors, γδ T cells were found in close proximity to NODAL-expressing tumor cells. Migration of γδ and αβ T cells was similar toward MDA-MB-231 cells in which NODAL had been knocked down (shN) and MDA-MB-231 scrambled control cells (shC). Furthermore, Vδ1 γδ T cells did not migrate preferentially toward conditioned medium from these cell lines. While 24-h exposure to NODAL did not impact CD69, PD-1, or T cell antigen receptor (TCR) expression on γδ T cells, long term exposure resulted in decreased Vδ2 TCR expression. Maturation of γδ T cells was not significantly influenced by NODAL stimulation. While neither short-nor long-term NODAL stimulation impacted the ability of γδ T cells to kill MCF-7 breast cancer cells, the absence of NODAL resulted in greater sensitivity of targets to γδ T cell cytotoxicity, while overexpression of NODAL conferred resistance. This appeared to be at least in part due to an inverse correlation between NODAL and surface MICA/B expression on breast cancer target lines. As such, it appears that NODAL may play a role in strategies employed by breast cancer cells to evade γδ T cell targeting, and this should be considered in the development of safe and effective γδ T cell immunotherapies.

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Targeting immune pathways in breast cancer: review of the prognostic utility of TILs in early stage triple negative breast cancer (TNBC)

Cited by 52 publications

References 19 publications

Correlation Between Mammographic Radiomics Features and the Level of Tumor-Infiltrating Lymphocytes in Patients With Triple-Negative Breast Cancer

Correlation Between Mammographic Radiomics Features and the Level of Tumor-Infiltrating Lymphocytes in Patients With Triple-Negative Breast Cancer

A Risk Scoring System Based on Tumor Microenvironment Cells to Predict Prognosis and Immune Activity in Triple-Negative Breast Cancer

Aberrantly Expressed Embryonic Protein NODAL Alters Breast Cancer Cell Susceptibility to γδ T Cell Cytotoxicity

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