Tumor Microenvironment Immunosuppression: A Roadblock to CAR T-Cell Advancement in Solid Tumors

Johnson, A.K.; Townsend, Michelle H.; O’Neill, Kim L.

doi:10.3390/cells11223626

Cited by 12 publications

(9 citation statements)

References 154 publications

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“…Immune cells in the tumor microenvironment play important roles in the occurrence and development of the tumor and are significantly associated with prognosis ( 28 , 29 ). They participate in remodeling the microenvironment, and regulating tumor progression; the tumor microenvironment affects immune cell infiltration ( 30 ), and targeting genes involved in this process is a promising strategy for tumor therapy.…”

Section: Discussionmentioning

confidence: 99%

Role of prognostic gene DKK1 in oral squamous cell carcinoma

Liu,

Wei,

Wang

et al. 2023

Oncol Lett

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Oral squamous cell carcinoma (OSCC) is one of the most common squamous cell carcinomas of the head and neck. The morbidity and mortality rates of OSCC have increased in recent years. However, the pathogenesis of this disease remains unknown. The present study aimed to identify predictive biomarkers and therapeutic targets for OSCC. Bioinformatics screening of differentially expressed genes in OSCC was performed based on data from The Cancer Genome Atlas and Gene Expression Omnibus databases. Dickkopf Wnt signaling pathway inhibitor 1 (DKK1) was identified to be associated with survival, tumor immunity and DNA repair in OSCC. Furthermore, the effects of DKK1 were evaluated by the knockdown of DKK1 in two OSCC cell lines. The proliferation, clonogenicity, migration and invasion of the cells were assessed in vitro using Cell Counting Kit-8, colony formation, wound healing and Transwell assays, respectively, and were found to be inhibited by DKK1 knockdown. The present study suggests that DKK1 may be used in the prognosis of patients with OSCC and that targeting DKK1 is a potential strategy for OSCC therapy.

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Section: Discussionmentioning

confidence: 99%

Role of prognostic gene DKK1 in oral squamous cell carcinoma

Liu,

Wei,

Wang

et al. 2023

Oncol Lett

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“…Since the first CAR T cell treatment was approved by the FDA in 2017, there have been five further approved treatments to date (Hamieh et al, 2023). CAR T cells specifically target tumor associated, or tumorspecific antigens to selectively kill the cancer (target) cells (Johnson et al, 2022). This property can allow for TME mediation by, for example, eliminating tumor associated macrophages which in turn delays tumor progression and prolonging survival (Rodriguez-Garcia et al, 2021).…”

Section: Cell Therapy For Targeting the Tmementioning

confidence: 99%

The road after cancer: biomaterials and tissue engineering approaches to mediate the tumor microenvironment post-cancer treatment

Westwood,

Nixon,

Emmerson

et al. 2024

Front. Biomater. Sci.

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Cancer affects tens of millions of the world’s population each year with a stark mortality rate. It is well established that in order to be effective in treating solid tumor cancers, the current treatment methods used often sacrifice surrounding healthy tissue and cause damage at the site of treatment, inducing changes to the surrounding microenvironment. These changes to the microenvironment can lead to adverse side effects as well as long-term damage which continues to have a detrimental impact on the patient’s quality of life, even after remission. It is believed that by modulating the tumor microenvironment (TME) post-treatment, not only may the efficacy of current treatments be improved, but such associated negative side effects, as well as further complications arising from treatment, including metastasis, have the potential to be reduced. Mediating the microenvironment is also considered to aid in repairing the damaged site post-treatment, subsequently making the conditions more favourable for promoting regenerative processes. This review provides a brief overview of the alterations in the TME resulting from the three main cancer treatments–chemotherapy, radiation therapy and surgery–and the most common tissue engineering methods currently used in an attempt to mediate the TME post-cancer therapy. Furthermore, it investigates new emerging technologies within this field and the progress of such methods in terms of reaching the clinical setting.

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“…Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) is one of the effective strategies to activate antitumor immunity, which has made great progress in treating a wide range of malignancies in recent years 157 . However, the effectiveness of immunotherapy is severely affected by the immunosuppression of microenvironment 158 . In addition, TME also plays an important role in immunosuppression to aggravate cancer proliferation and metastasis.…”

Section: Cdt-based Combination Therapymentioning

confidence: 99%

Multifunctional nanomedicines-enabled chemodynamic-synergized multimodal tumor therapy via Fenton and Fenton-like reactions

H¹,

Cao²,

Liu³

et al. 2023

Theranostics

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Chemodynamic therapy (CDT) is well-known for using the tumor microenvironment to activate the Fenton reaction or Fenton-like reaction to generate strong oxidative hydroxyl radicals for tumor-specific treatment. It is highly selective and safe, without depth limitation of tissue penetration, and shows its potential as a new green therapeutic method with great clinical application. However, the catalytic efficiency of reagents involved in the Fenton reaction is severely affected by the inherent microenvironmental limitations of tumors and the strict Fenton reaction-dependent conditions. With the increasing application of nanotechnology in the medical field, combined therapies based on different types of functional nanomaterials have opened up new avenues for the development of next-generation CDT-enhanced system. This review will comprehensively exemplify representative results of combined therapies of CDT with other antitumor therapies such as chemotherapy, phototherapy, sonodynamic therapy, radiation therapy, magnetic hyperthermia therapy, immunotherapy, starvation therapy, gas therapy, gene therapy, oncosis therapy, or a combination thereof for improving antitumor efficiency from hundreds of the latest literature, introduce strategies such as the ingenious design of nanomedicines and tumor microenvironment regulations to enhance the combination therapy, and further summarize the challenges and future perspective of CDT-based multimodal anticancer therapy.

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Tumor Microenvironment Immunosuppression: A Roadblock to CAR T-Cell Advancement in Solid Tumors

Cited by 12 publications

References 154 publications

Role of prognostic gene DKK1 in oral squamous cell carcinoma

Role of prognostic gene DKK1 in oral squamous cell carcinoma

The road after cancer: biomaterials and tissue engineering approaches to mediate the tumor microenvironment post-cancer treatment

Multifunctional nanomedicines-enabled chemodynamic-synergized multimodal tumor therapy via Fenton and Fenton-like reactions

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