Fates of CD8+ T cells in Tumor Microenvironment

Maimela, Nomathamsanqa Resegofetse; Li, Shasha; Zhang, Yi

doi:10.1016/j.csbj.2018.11.004

Cited by 374 publications

(280 citation statements)

References 173 publications

(247 reference statements)

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“…Interestingly, significantly higher levels of multiple cytokines associated with cytotoxic Tcell recruitment and infiltration (CCL5, ICAM-1) (Maimela, Liu et al, 2019) were detected in BT474-secreted media (Fig. 4D), which is consistent with the observation of more infiltrated T cells in TrS patient samples.…”

Section: Trr Signature Predicts Tumor Progression Patient Overall Susupporting

confidence: 87%

Immunotherapy Implication of Signature-Guided Biomarker Discovery for Trastuzumab-Resistant HER2-Positive Breast Cancer

Sand¹,

At²,

Gt³

et al. 2020

Preprint

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Despite the great improvement of patient outcomes by trastuzumab, a monoclonal antibody targeted on HER2-positive breast cancer, approximately 23% of patients with early-stage disease treated with adjuvant trastuzumab either fail to respond or experience recurrence within 10 years, highlighting the importance of identifying which HER2-positive patients would benefit from trastuzumab upfront. Efforts to identify biomarkers predictive of response to trastuzumab in initial breast tumor core biopsies have been complicated by the clinical and biological heterogeneity of HER2-positive tumors. Therefore, we identified a trastuzumab-resistant (TrR) signature that accurately predicts response to trastuzumab quantitively and qualitatively in vitro and in vivo, via repurposing transcriptome profiles in an engineered cell line model. We additionally demonstrated that our TrR signature was associated with tumor progression and capable of stratifying patient prognosis. Our study further illustrated the possible mechanism of this resistance as being less inherited cytotoxic T cell infiltration and failure to secrete Interferon-γ upon trastuzumab treatment in TrR tumors. These findings highlight the potential clinical application of TrR signature in treatment management and identifying possible immunotherapy interventions.

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Section: Trr Signature Predicts Tumor Progression Patient Overall Susupporting

confidence: 87%

Immunotherapy Implication of Signature-Guided Biomarker Discovery for Trastuzumab-Resistant HER2-Positive Breast Cancer

Sand¹,

At²,

Gt³

et al. 2020

Preprint

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show abstract

“…Many previous studies have addressed managing the hypoxic tumor using HIF and PD-L1 inhibitors which resulted in promising outcomes (91,106). It is well established that boosting the CD8+ cell infiltration into the tumor niche can reverse immune evasion (107)(108)(109)(110). Results from our experiments using PX-478 and Durvalumab on 3D-O matrices confirm that reversing lymphocyte functional impairment is possible by either targeting HIF-1α or targeting inhibitory checkpoint pathways like PD-L1/PD-1.…”

Section: Immune Cell Infiltration Into 3d Matrices Has Been Observedsupporting

confidence: 63%

Bioengineering a novel 3D in-vitro model to recreate physiological oxygen levels and tumor-immune interactions

Bhattacharya

Calar

Evans

et al. 2019

Preprint

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Oxygen deprivation within tumors is one of the most prevalent causes of resilient cancer cell survival and increased immune evasion in breast cancer (BCa). Current in vitro models do not adequately mimic physiological oxygen levels relevant to breast tissue and its tumor-immune interactions. Here, we propose an approach to engineer a three-dimensional (3D) model (named 3D engineered oxygen, 3D-O) that supports growth of BCa cells and generates physio-and pathophysiological oxygen levels. Low oxygen-induced changes within the 3D-O model supported known tumor hypoxia characteristics such as reduced BCa cell proliferation, increased extracellular matrix protein expression, increased extracellular vesicle secretion and enhanced immune surface marker expression on BCa cells. We further demonstrated that low oxygeninduced changes mimicked tumor-immune interactions leading to immune evasion mechanisms. CD8+ T cell infiltration was significantly impaired under pathophysiological oxygen levels andwe were able to establish that hypoxia inhibition re-sensitize BCa cells to cytotoxic CD8+ T cells.Therefore, our novel 3D-O model could serve as a promising platform for the evaluation of immunological events and as a drug-screening platform tool to overcome hypoxia-driven immune evasion.

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“…T lymphocytes play a prominent role in the response to tumors; specifically in TME, by interacting with cancer cells and secreted factors, T cells became dysfunctional and exhibit decreased viability and proliferation and impaired effector functions [54]. In particular, CD8+ cytotoxic T lymphocytes are compromised in numerous cancer types [55] and several lines of evidence described EVs as mediators of the CD8+T cell growth inhibition ( Figure 1B). EVs from head and neck squamous cell carcinoma and melanoma contained FasL and MHC class I molecules and significantly inhibit the expansion of primary-activated CD8+ T cells; consistent with these findings, authors showed that tumor EVs induce CD8+ Jurkat cells death [56].…”

Section: Tevs and T Lymphocyte Cellsmentioning

confidence: 99%

Extracellular Vesicles and Tumor-Immune Escape: Biological Functions and Clinical Perspectives

Raimondo

Pucci

Alessandro

et al. 2020

IJMS

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The modulation of the immune system is one of the hallmarks of cancer. It is now widely described that cancer cells are able to evade the immune response and thus establish immune tolerance. The exploration of the mechanisms underlying this ability of cancer cells has always attracted the scientific community and is the basis for the development of new promising cancer therapies. Recent evidence has highlighted how extracellular vesicles (EVs) represent a mechanism by which cancer cells promote immune escape by inducing phenotypic changes on different immune cell populations. In this review, we will discuss the recent findings on the role of tumor-derived extracellular vesicles (TEVs) in regulating immune checkpoints, focusing on the PD-L1/PD-1 axis.

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Fates of CD8+ T cells in Tumor Microenvironment

Cited by 374 publications

References 173 publications

Immunotherapy Implication of Signature-Guided Biomarker Discovery for Trastuzumab-Resistant HER2-Positive Breast Cancer

Immunotherapy Implication of Signature-Guided Biomarker Discovery for Trastuzumab-Resistant HER2-Positive Breast Cancer

Bioengineering a novel 3D in-vitro model to recreate physiological oxygen levels and tumor-immune interactions

Extracellular Vesicles and Tumor-Immune Escape: Biological Functions and Clinical Perspectives

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