Role of the immunosuppressive microenvironment in immunotherapy

Tormoen, Garth W.; Crittenden, Marka R.; Gough, Michael

doi:10.1016/j.adro.2018.08.018

Cited by 128 publications

(93 citation statements)

References 94 publications

(82 reference statements)

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“…Cancer immunotherapy is changing cancer treatment paradigms, but response rates to several existing treatment types remain low. This at least partially can be explained by the lack of host's pre-existing anti-tumor immunity (57,58). Moreover, one of the cancer hallmarks is the avoidance of the immune system's potential attack, the escape from the immune control, and remain invisible to the immune cells (57).…”

Section: Immunosuppression-reducing Treatmentsmentioning

confidence: 99%

“…This at least partially can be explained by the lack of host's pre-existing anti-tumor immunity (57,58). Moreover, one of the cancer hallmarks is the avoidance of the immune system's potential attack, the escape from the immune control, and remain invisible to the immune cells (57). It is important to remember that tumor is composed of cancer cells, but also stromal features, such as fibroblasts, blood vessels and infiltrating immune cells among others (57).…”

Section: Immunosuppression-reducing Treatmentsmentioning

confidence: 99%

“…Moreover, one of the cancer hallmarks is the avoidance of the immune system's potential attack, the escape from the immune control, and remain invisible to the immune cells (57). It is important to remember that tumor is composed of cancer cells, but also stromal features, such as fibroblasts, blood vessels and infiltrating immune cells among others (57). All those elements are collectively named tumor microenvironment (TME) and remain of utmost importance for the immunotherapy success (57,58).…”

Section: Immunosuppression-reducing Treatmentsmentioning

confidence: 99%

“…It is important to remember that tumor is composed of cancer cells, but also stromal features, such as fibroblasts, blood vessels and infiltrating immune cells among others (57). All those elements are collectively named tumor microenvironment (TME) and remain of utmost importance for the immunotherapy success (57,58). Tumor intrinsic immunosuppressive features can also inhibit effector T cell function, especially regions of hypoxia or elevated lactate levels in the TME (57,59).…”

Section: Immunosuppression-reducing Treatmentsmentioning

confidence: 99%

“…All those elements are collectively named tumor microenvironment (TME) and remain of utmost importance for the immunotherapy success (57,58). Tumor intrinsic immunosuppressive features can also inhibit effector T cell function, especially regions of hypoxia or elevated lactate levels in the TME (57,59). In fact, TME is highly variable between individuals and different tumors themselves, therefore many preclinical and clinical trials are targeting novel targets related to the TME, especially the TME-mediated immunosuppressive pathways (57,58,60).…”

Section: Immunosuppression-reducing Treatmentsmentioning

confidence: 99%

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The Intriguing History of Cancer Immunotherapy

2019

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Immunotherapy is often perceived as a relatively recent advance. In reality, however, one should be looking for the beginnings of cancer immunotherapy under different names as far as in the Antiquity. The first scientific attempts to modulate patients' immune systems to cure cancer can be attributed to two German physicians, Fehleisen and Busch, who independently noticed significant tumor regression after erysipelas infection. The next significant advances came from William Bradley Coley who is known today as the Father of Immunotherapy. It was Coley who first attempted to harness the immune system for treating bone cancer in 1891. His achievements were largely unnoticed for over fifty years, and several seminal discoveries in the field of Immunology, such as the existence of T cells and their crucial role in immunity in 1967, stepped up the research toward cancer immunotherapy known today. The following paper tracks cancer immunotherapy from its known beginnings up until recent events, including the 2018 Nobel Prize award to James Allison and Tasuku Honjo for their meticulous work on checkpoint molecules as potential therapeutic targets. That work has led to the successful development of new checkpoint inhibitors, CAR T-cells and oncolytic viruses and the pace of such advances brings the highest hope for the future of cancer treatment.

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Section: Immunosuppression-reducing Treatmentsmentioning

confidence: 99%

Section: Immunosuppression-reducing Treatmentsmentioning

confidence: 99%

Section: Immunosuppression-reducing Treatmentsmentioning

confidence: 99%

Section: Immunosuppression-reducing Treatmentsmentioning

confidence: 99%

Section: Immunosuppression-reducing Treatmentsmentioning

confidence: 99%

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The Intriguing History of Cancer Immunotherapy

2019

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CAR‐T Therapy in Clinical Practice: Technical Advances and Current Challenges

et al. 2022

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Over the last two decades, basic research and clinical investigations have achieved tremendous progress in the field of cancer immunotherapies. Chimeric antigen receptor (CAR)-T cell therapy has shown revolutionary clinical success in patients with relapsed/refractory (R/R) B cell hematological malignancies by targeting homogeneously expressed antigens. [1] CARs are synthetic receptors, expressed on the surface of allogeneic or autologous T cells, and capable of redirecting genetically modified T cells to combat and destroy immune escaped tumor cells. This is achieved by a major histocompatibility complex (MHC)-independent manner. [2] The first two genetically engineered CD19targeted CAR-T cell therapies, Kymriah (Tisagenlecleucel, Novatis) and Yescarta (Axicabtagene Ciloleucel, Kite Pharma), were approved in 2017 by the US Food and Drug Administration (FDA). [1a,3] Subsequently, Tecartus (brexucabtagene Autoleucel, Kite Pharma) was approved for mantle cell lymphoma (MCL) in July, 2020, Breyanzi (lisocabtagene maraleucel, Juno Therapeutics) was approved for diffuse large B-cell lymphoma (DLBCL) in February, 2021 and Abecma (idecabtagene vicleucel, Bluebird Bio) later in March, 2021. The information of the approved 5 CAR-T drugs is summarized from https://www.fda.gov/ (Table 1). The CAR-T treatments were successively approved by the European Union, the United Kindom, and Canada in 2018, and finally China in 2021.We summarized the data on the clinicaltrials.gov website with the keyword "CAR" and excluded the non-cellular therapies manually. As of Dec 31, 2021, ≈900 CAR-T cell clinical trials have been registered and conducted all over the world. [1b,4] (Figure 1A) Although some clinical trials are not registered on the clinical trials website due to the local rules, we can still analyze the development tendency. Currently, the United States and China are the top two leading countries for CAR-T therapy clinical research. Over 90% of CAR-T clinical trials are initiated in these two countries. The United States has 326 registered clinical trials completed or in progress since 2003 and 58 clinical studies are posted in 2021. China is the fastest-growing country when it comes to CAR-T clinical research. Although the first CAR-T cell clinical trial was Chimeric antigen receptors (CAR) redirect T cells to specifically recognize and eliminate tumor cells. CAR-T therapy has achieved successful clinical outcomes, and it has been transformed into commercially available products to treat acute lymphoblastic leukemia and B cell lymphoma. These breakthroughs have motivated hundreds of CAR-T clinical trials initiated each year, with ≈900 cases registered on the ClinicalTrials website till 2021. Accumulating clinical experiences have highlighted some limitations of this strategy, e.g., relapse after complete response, poor efficacy in solid tumors, on-target off-tumor toxicities, lack of persistence, and tumor resistance. These challenges limit the therapeutic application of CAR-T cells. Multi disciplinary approaches are activel...

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A 3D Bioprinted Human Neurovascular Unit Model of Glioblastoma Tumor Growth

Tung,

Chen,

Derr

et al. 2024

Adv Healthcare Materials

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A 3D bioprinted neurovascular unit (NVU) model was developed to study glioblastoma (GBM) tumor growth in a brain‐like microenvironment. The NVU model included human primary astrocytes, pericytes and brain microvascular endothelial cells, and patient‐derived glioblastoma cells (JHH‐520) were used for this study. We used fluorescence reporters with confocal high content imaging to quantitate real‐time microvascular network formation and tumor growth. Extensive validation of the NVU‐GBM model included immunostaining for brain relevant cellular markers and extracellular matrix components; single cell RNA sequencing to establish physiologically relevant transcriptomics changes; and secretion of NVU and GBM‐relevant cytokines. The scRNAseq revealed changes in gene expression and cytokines secretion associated with wound healing/angiogenesis, including the appearance of an endothelial mesenchymal transition (EndMT) cell population. The NVU‐GBM model was used to test 18 chemotherapeutics and anti‐cancer drugs to assess the pharmacological relevance of the model and robustness for high throughput screening.This article is protected by copyright. All rights reserved

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Role of the immunosuppressive microenvironment in immunotherapy

Cited by 128 publications

References 94 publications

The Intriguing History of Cancer Immunotherapy

The Intriguing History of Cancer Immunotherapy

CAR‐T Therapy in Clinical Practice: Technical Advances and Current Challenges

A 3D Bioprinted Human Neurovascular Unit Model of Glioblastoma Tumor Growth

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