Immune checkpoint inhibitors: Key trials and an emerging role in breast cancer

Gaynor, Nicola; Crown, John; Collins, Denis M.

doi:10.1016/j.semcancer.2020.06.016

Cited by 125 publications

(106 citation statements)

References 147 publications

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“…Within the BC TME, BC cells are described to express ligands such as programmed death-ligand 1 (PD-L1) at their surface or increase the surface expression of receptors like cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) in T cells [ 24 ]. These immune checkpoints sustain the binding of BC cells with immune cells, suppressing the inflammatory and tumoricidal functions of the latter [ 24 ]. In the light of the discovery of immune checkpoints, several breakthroughs have been achieved in recent decades [ 25 , 26 ].…”

Section: Tumour-associated Macrophages Within the Breast Cancer MImentioning

confidence: 99%

Cracking the Breast Cancer Glyco-Code through Glycan-Lectin Interactions: Targeting Immunosuppressive Macrophages

Lopes

Correia

Palma

et al. 2021

IJMS

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The immune microenvironment of breast cancer (BC) is composed by high macrophage infiltrates, correlated with the most aggressive subtypes. Tumour-associated macrophages (TAM) within the BC microenvironment are key regulators of immune suppression and BC progression. Nevertheless, several key questions regarding TAM polarisation by BC are still not fully understood. Recently, the modulation of the immune microenvironment has been described via the recognition of abnormal glycosylation patterns at BC cell surface. These patterns rise as a resource to identify potential targets on TAM in the BC context, leading to the development of novel immunotherapies. Herein, we will summarize recent studies describing advances in identifying altered glycan structures in BC cells. We will focus on BC-specific glycosylation patterns known to modulate the phenotype and function of macrophages recruited to the tumour site, such as structures with sialylated or N-acetylgalactosamine epitopes. Moreover, the lectins present at the surface of macrophages reported to bind to such antigens, inducing tumour-prone TAM phenotypes, will also be highlighted. Finally, we will discuss and give our view on the potential and current challenges of targeting these glycan-lectin interactions to reshape the immunosuppressive landscape of BC.

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Section: Tumour-associated Macrophages Within the Breast Cancer MImentioning

confidence: 99%

Cracking the Breast Cancer Glyco-Code through Glycan-Lectin Interactions: Targeting Immunosuppressive Macrophages

Lopes

Correia

Palma

et al. 2021

IJMS

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“…China. 2 The Third Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, P.R. China.…”

Section: Acknowledgmentsmentioning

confidence: 99%

“…TNBC is the most aggressive subtype, and it is not sensitive to hormone and targeted therapy. Chemotherapy remains the standard treatment for TNBC because of the lack of targeted therapies 2,3 . Therefore, there is an urgent need to deepen our understanding of the pathogenesis of breast cancer and identify new treatment strategies.…”

Section: Introductionmentioning

confidence: 99%

Ruanjian Sanjie Decoction Induces Apoptosis in Triple-negative Breast Cancer Cells by Downregulating cIAP1/2 and XIAP

Zhao¹,

Wang²,

Jia³

et al. 2020

Preprint

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Background: Traditional Chinese medicine (TCM) comprises a unique theoretical system developed over thousands of years. The previous study reported that Ruanjian Sanjie (RJSJ) exerts anti-tumor effects by inducing cell apoptosis. However, the mechanism is not clear. Methods: In this study, we investigated the possible mechanism by the strategy of combining network pharmacology analysis with experiment (in vitro and in vivo). First, four kinds of breast cancer cell lines were used to conduct proliferation, apoptosis and cell cycle analysis. Secondly, to study pathophysiological processes of breast cancer at the molecular network level, we for the first time constructed an “integrated apoptosis module network of breast cancer” by assembling the regulatory relationships of canonical apoptosis signaling pathways. Through the strategy of combining network analysis and experiments, we analyzed the main mechanism of RJSJ in breast cancer and screened out the core genes. We further studied the inhibitory effect of RJSJ combined with carboplatin (CBP) in vivo. Finally, the synergistic effect of RJSJ and CBP were analyzed and the potential active components in RJSJ were predicted.Results: This study demonstrated that RJSJ could significantly inhibit breast cancer cell proliferation and induce apoptosis in a concentration-dependent manner. The primary mechanism of RJSJ in the treatment of breast cancer was pro-apoptotic. The core apoptosis genes regulated by RJSJ were cIAP1/2 and XIAP. We also found that RJSJ in combination with CBP tended to synergistically induce apoptosis, which might mainly be achieved through the regulation of multiple targets and pathways. Alexandrin (BX05, XKC02, SCG01), baicalin (BX22), guanosine (BX32), arjunglucoside I (XKC10) etc. were predicted as potential active components.Conclusions: These findings provide the rationale for exploring the therapeutic effects of RJSJ against breast cancer and providing a bridge for the combined use of Chinese and Western medicine.

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“…Numerous types of cancer immunotherapy are being trialed and implemented, as reviewed in detail elsewhere (7). Immune checkpoint blockade (ICB) has progressed most prominently as an effective immunotherapy by targeting inhibitory T cell regulatory molecules such as programmed cell death-1 (PD-1), its ligands programmed cell death ligand 1/2 (PD-L1/L2), and cytotoxic T-lymphocyte associated antigen-4 (CTLA-4), thereby re-invigorating the anti-tumor immune response (8). In 2019, the US Food and Drug Administration (FDA) approved the use of Atezolizumab, a blocking antibody targeting PD-L1, in combination with nab-paclitaxel chemotherapy for first-line treatment of unresectable, PD-L1 positive, locally advanced, or metastatic TNBC.…”

Section: Introductionmentioning

confidence: 99%

Lactate Metabolism and Immune Modulation in Breast Cancer: A Focused Review on Triple Negative Breast Tumors

Belič

Decock

2020

Front. Oncol.

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Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer associated with poor prognosis, early recurrence, and the lack of durable chemotherapy responses and specific targeted treatments. The recent FDA approval for immune checkpoint inhibition in combination with nab-paclitaxel for the treatment of metastatic TNBC created opportunity to advocate for immunotherapy in TNBC patients. However, improving the current low response rates is vital. Most cancers, including TNBC tumors, display metabolic plasticity and undergo reprogramming into highly glycolytic tumors through the Warburg effect. Consequently, accumulation of the metabolic byproduct lactate and extracellular acidification is often observed in several solid tumors, thereby exacerbating tumor cell proliferation, metastasis, and angiogenesis. In this review, we focus on the role of lactate acidosis in the microenvironment of glycolytic breast tumors as a major driver for immune evasion with a special emphasis on TNBCs. In particular, we will discuss the role of lactate regulators such as glucose transporters, lactate dehydrogenases, and lactate transporters in modulating immune functionality and checkpoint expression in numerous immune cell types. This review aims to spark discussion on interventions targeting lactate acidosis in combination with immunotherapy to provide an effective means of improving response to immune checkpoint inhibitors in TNBC, in addition to highlighting challenges that may arise from TNBC tumor heterogeneity.

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Immune checkpoint inhibitors: Key trials and an emerging role in breast cancer

Cited by 125 publications

References 147 publications

Cracking the Breast Cancer Glyco-Code through Glycan-Lectin Interactions: Targeting Immunosuppressive Macrophages

Cracking the Breast Cancer Glyco-Code through Glycan-Lectin Interactions: Targeting Immunosuppressive Macrophages

Ruanjian Sanjie Decoction Induces Apoptosis in Triple-negative Breast Cancer Cells by Downregulating cIAP1/2 and XIAP

Lactate Metabolism and Immune Modulation in Breast Cancer: A Focused Review on Triple Negative Breast Tumors

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