The combined presence of CD20 + B cells and PD-L1 + tumor-infiltrating lymphocytes in inflammatory breast cancer is prognostic of improved patient outcome

Arias-Pulido, Hugo; Cimino‐Mathews, Ashley; Chaher, Nabila; Qualls, Clifford; Joste, Nancy E.; Colpaert, Cécile; Marotti, Jonathan D.; Foisey, Maxwell Gabriel; Prossnitz, Eric R.; Emens, Leisha A.; Fiering, Steven

doi:10.1007/s10549-018-4834-7

Cited by 61 publications

(72 citation statements)

References 33 publications

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“…In addition, it has been reported that PD‐L1 is differentially expressed across different BC subtypes. In particular, available evidence consistently reports greater expression of PD‐L1 in the TN subtype (up to 60% of PD‐L1 expression) compared with non‐TNBC . These data appear to be coherent with the observation that PD‐L1 tumor expression is positively associated with stromal tumor‐infiltrating lymphocytes (TILs) in this BC subtype , which is known to be more frequently infiltrated by stromal TILs than non‐TNBC , as summarized in Table , thus possibly suggesting that these two immune biomarkers tend to run parallel.…”

Section: Methodssupporting

confidence: 74%

“…Data on PD‐L1 expression in HER2‐positive BC are more controversial. In fact, whereas in some studies HER2 positivity has been correlated with higher expression of PD‐L1 (up to 50%) compared with HER2‐negative BC , others failed to report any difference .…”

Section: Methodsmentioning

confidence: 93%

“…In particular, PD‐L1 expression has been positively and independently associated with DFS/RFS and/or OS in several unselected primary BC cohorts . In addition, when considering specific BC subtypes, it has been suggested that PD‐L1 protein expression may retain a positive prognostic role in TNBC and in HER2+ BC, in both trastuzumab‐treated and untreated patients .…”

Section: Methodsmentioning

confidence: 99%

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Programmed Cell Death Ligand 1 in Breast Cancer: Technical Aspects, Prognostic Implications, and Predictive Value

2019

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In the light of recent advances in the immunotherapy field for breast cancer (BC) treatment, especially in the triple‐negative subtype, the identification of reliable biomarkers capable of improving patient selection is paramount, because only a portion of patients seem to derive benefit from this appealing treatment strategy. In this context, the role of programmed cell death ligand 1 (PD‐L1) as a potential prognostic and/or predictive biomarker has been intensively explored, with controversial results. The aim of the present review is to collect available evidence on the biological relevance and clinical utility of PD‐L1 expression in BC, with particular emphasis on technical aspects, prognostic implications, and predictive value of this promising biomarker. Implications for Practice In the light of the promising results coming from trials of immune checkpoint inhibitors for breast cancer treatment, the potential predictive and/or prognostic role of programmed cell death ligand 1 (PD‐L1) in breast cancer has gained increasing interest. This review provides clinicians with an overview of the available clinical evidence regarding PD‐L1 as a biomarker in breast cancer, focusing on both data with a possible direct impact on clinic and methodological pitfalls that need to be addressed in order to optimize PD‐L1 implementation as a clinically useful tool for breast cancer management.

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Section: Methodssupporting

confidence: 74%

Section: Methodsmentioning

confidence: 93%

Section: Methodsmentioning

confidence: 99%

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Programmed Cell Death Ligand 1 in Breast Cancer: Technical Aspects, Prognostic Implications, and Predictive Value

2019

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“…[21]. It has also been demonstrated that significant anti-CSC immunity was induced by dendritic cell vaccine basing on CSC both in vitro and in immune-competent hosts [8,22]. B lymphocytes were recently found to play a pivotal role in the cancer immune by being an assistant for T lymphocyte [23].…”

Section: Discussionmentioning

confidence: 99%

Identification of immune-related therapeutically relevant biomarkers in breast cancer and breast cancer stem cells by transcription-wide analysis: a clinical prospective study

Wang

Liu

et al. 2020

Preprint

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Background: Cancer stem cells (CSCs) represent a subset of tumor cells that are responsible for recurrence and metastasis of tumors. These cells are resistant to radiotherapy and chemotherapy. Immunotherapeutic strategies that target CSCs specifically have provided initial results; however, the mechanism of action of these strategies is unclear. Methods: The data were requested from The Cancer Genome Atlas and Genotype-Tissue Expression, followed with the survival analysis and weighted gene co-expression network analysis to detect survival- and stemness-related genes. Patients were divided into three groups based on their immune status by applying ssGSEA with proven dependability by ESTIMATE analysis. The filtered key genes were analyzed using oncomine, qRT-PCR, and functional analysis. Results: Patients in a group with a higher stemness and a lower immune infiltration showed a worse overall survival probability, stemness and immune infiltration characteristics of breast cancer progressed in a non-linear fashion. Thirteen key genes related to stemness and immunity were identified and the functional analysis indicated their crucial roles in cell proliferation and immune escape strategies. The qRT-PCR results showed that the expression of PIMREG and MTFR2 differed in different stages of patients. Conclusions: Our study revealed a promising potential for CSC-target immunotherapy in the early stage of cancer and a probable value for PIMREG and MTFR2 as biomarkers and targets for immunotherapy. Trial registration: This study protocol registered with Chinese Clinical Trial Registry (http://www.chictr.org.cn/showproj.aspx?proj=19710; Date of registration: 25/09/2017; Registration number: ChiCTR-PDN-17012784) and was approved by the ethical committee of Affiliated Hospital of Chongqing Medical University (approval number: 2020-119). Keywords: breast cancer, cancer stem cell, tumor immune infiltration, PIMREG, MTFR2.

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“…Coexistence of CD20+ TILs and PD-L1+ tumour cells were significantly associated with better DOI: 10.1159/000504055 survival,a high pCR rate, and high infiltration of TILs in triple-negative IBC. High CD20+ and PD-L1+ TIL infiltration correlated with fewer relapses, a high pCR, and higher rates of DFS and BCSS [42]. PD-L1 expression in tumour cells was positively associated with a high infiltration of intratumoural/peritumoural CD8+ TILs and CD163+ macrophages in HER2-positive breast cancer [43].…”

Section: Cd20+til and Pdl-1 Expression In Breast Cancermentioning

confidence: 93%

The Immune Microenvironment in Breast Carcinoma: Predictive and Prognostic Role in the Neoadjuvant Setting

2019

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The immune system is responsible for the maintenance of tissue homeostasis by initiating inflammatory reactions that involve the activation of innate and adaptive immune cells.• In cancer, immune responses that aim to eliminate the tumour are elicited. However, the neoplastic cells may escape the immune control through immune-editing which depends on both tumour and immune cell interactions. • New therapies have the potential to reactivate the immune response against cancer, e.g., in melanomas and lung cancer, and this is associated with improved outcomes. Novel Insights• Immune cell subpopulations, especially tumour-infiltrating lymphocytes (TILs) in the breast carcinoma microenvironment, can influence the tumour response to various neoadjuvant chemotherapy regimens, particularly in triple-negative and HER2-positive breast cancers. • Recognition of TIL subtypes and locations in relation to tumour cells in breast carcinoma are promising for the development of more effective options of targeted therapy. • The International TILs Working Group recommends the assessment of TILs on H&E sections. StromalTILs should be analysed excluding necrotic and crushed areas. Immunohistochemical and digital assessments of TILs are currently limited to the research setting. AbstractThe prognostic value of the immune cell infiltrate in the breast carcinoma microenvironment is still uncertain. We reviewed published articles analysing the infiltration of inflammatory cells in the microenvironment of breast carcinoma. Data revealed the importance of infiltration of these immune cells in the prognosis of breast carcinoma, particularly the triple-negative and HER2-positive phenotypes. Tumourinfiltrating lymphocytes and their subtypes play a fundamental role in predicting the pathological complete response (pCR) to neoadjuvant chemotherapy. More research aiming to dissect a complex network of communication between cancer cells and other cellular components of the tumour microenvironment is necessary to develop more effective therapeutic approaches.

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The combined presence of CD20 + B cells and PD-L1 + tumor-infiltrating lymphocytes in inflammatory breast cancer is prognostic of improved patient outcome

Cited by 61 publications

References 33 publications

Programmed Cell Death Ligand 1 in Breast Cancer: Technical Aspects, Prognostic Implications, and Predictive Value

Programmed Cell Death Ligand 1 in Breast Cancer: Technical Aspects, Prognostic Implications, and Predictive Value

Identification of immune-related therapeutically relevant biomarkers in breast cancer and breast cancer stem cells by transcription-wide analysis: a clinical prospective study

The Immune Microenvironment in Breast Carcinoma: Predictive and Prognostic Role in the Neoadjuvant Setting

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