Unleashing Tumour-Dendritic Cells to Fight Cancer by Tackling Their Three A’s: Abundance, Activation and Antigen-Delivery

Murgaski, Aleksandar; Bardet, Pauline M. R.; Arnouk, Sana M.; Clappaert, Emile J.; Laoui, Damya

doi:10.3390/cancers11050670

Cited by 15 publications

(22 citation statements)

References 108 publications

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“…These studies emphasize the importance of functional DCs in effective intra-tumoral DC-T cell crosstalk for immunotherapy response. Therefore, targeting T cells without taking into account and resolving DC dysfunction might hamper the success of T cell-centered immunotherapies in CRC (198,199).…”

Section: Tumor-induced DC Dysfunction and Immunotherapy Efficacymentioning

confidence: 99%

The Therapeutic Potential of Tackling Tumor-Induced Dendritic Cell Dysfunction in Colorectal Cancer

Subtil¹,

Cambi²,

Tauriello³

et al. 2021

Front. Immunol.

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Colorectal cancer (CRC) is the third most diagnosed malignancy and the second leading cause of cancer-related deaths worldwide. Locally advanced and metastatic disease exhibit resistance to therapy and are prone to recurrence. Despite significant advances in standard of care and targeted (immuno)therapies, the treatment effects in metastatic CRC patients have been modest. Untreatable cancer metastasis accounts for poor prognosis and most CRC deaths. The generation of a strong immunosuppressive tumor microenvironment (TME) by CRC constitutes a major hurdle for tumor clearance by the immune system. Dendritic cells (DCs), often impaired in the TME, play a critical role in the initiation and amplification of anti-tumor immune responses. Evidence suggests that tumor-mediated DC dysfunction is decisive for tumor growth and metastasis initiation, as well as for the success of immunotherapies. Unravelling and understanding the complex crosstalk between CRC and DCs holds promise for identifying key mechanisms involved in tumor progression and spread that can be exploited for therapy. The main goal of this review is to provide an overview of the current knowledge on the impact of CRC-driven immunosuppression on DCs phenotype and functionality, and its significance for disease progression, patient prognosis, and treatment response. Moreover, present knowledge gaps will be highlighted as promising opportunities to further understand and therapeutically target DC dysfunction in CRC. Given the complexity and heterogeneity of CRC, future research will benefit from the use of patient-derived material and the development of in vitro organoid-based co-culture systems to model and study DCs within the CRC TME.

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Section: Tumor-induced DC Dysfunction and Immunotherapy Efficacymentioning

confidence: 99%

The Therapeutic Potential of Tackling Tumor-Induced Dendritic Cell Dysfunction in Colorectal Cancer

Subtil¹,

Cambi²,

Tauriello³

et al. 2021

Front. Immunol.

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“…This binding pattern was reflected in their biodistribution when labeled with 99m Tc, with DC2.1 showing accumulation in liver, spleen and lungs, and DC1.8 primarily showing signals in skin. With the growing interest in targeting tumor-associated DCs to unleash an antitumor immune response, further studies on the potential of DC-targeting nanobodies to image specific DC subsets is warranted 120.…”

Section: Nanobodies Represent a Versatile Platform For Imaging Of Canmentioning

confidence: 99%

Theranostics in immuno-oncology using nanobody derivatives

Lecocq

Vlaeminck

Hanssens³

et al. 2019

Theranostics

101

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Targeted therapy and immunotherapy have become mainstream in cancer treatment. However, only patient subsets benefit from these expensive therapies, and often responses are short‐lived or coincide with side effects. A growing modality in precision oncology is the development of theranostics, as this enables patient selection, treatment and monitoring. In this approach, labeled compounds and an imaging technology are used to diagnose patients and select the best treatment option, whereas for therapy, related compounds are used to target cancer cells or the tumor stroma. In this context, nanobodies and nanobody-directed therapeutics have gained interest. This interest stems from their high antigen specificity, small size, ease of labeling and engineering, allowing specific imaging and design of therapies targeting antigens on tumor cells, immune cells as well as proteins in the tumor environment. This review provides a comprehensive overview on the state-of-the-art regarding the use of nanobodies as theranostics, and their importance in the emerging field of personalized medicine.

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“…Although the immune-stimulatory potential of lung DC can have protective effects in cancer, the lung TME inhibits their antitumor functions ( figure 2 ), and efforts are underway to test the efficacy of combining a DC-based vaccine with CBT. 69 The protective role of cDC1 is clearly illustrated in studies of mouse models of lung adenocarcinoma: increasing lung cDC1 number results in a reduced tumor burden, while deleting them causes a lack of CD8 + T cell infiltration and increased tumor progression. 70 71 The presence of a cDC1 gene signature is also associated with better outcomes in patients with lung adenocarcinoma.…”

Section: Myeloid Apc In Cbt-sensitive Carcinomasmentioning

confidence: 99%

Impact of anatomic site on antigen-presenting cells in cancer

Zagorulya

Duong

Spranger

2020

J Immunother Cancer

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Checkpoint blockade immunotherapy (CBT) can induce long-term clinical benefits in patients with advanced cancer; however, response rates to CBT vary by cancer type. Cancers of the skin, lung, and kidney are largely responsive to CBT, while cancers of the pancreas, ovary, breast, and metastatic lesions to the liver respond poorly. The impact of tissue-resident immune cells on antitumor immunity is an emerging area of investigation. Recent evidence indicates that antitumor immune responses and efficacy of CBT depend on the tissue site of the tumor lesion. As myeloid cells are predominantly tissue-resident and can shape tumor-reactive T cell responses, it is conceivable that tissue-specific differences in their function underlie the tissue-site-dependent variability in CBT responses. Understanding the roles of tissue-specific myeloid cells in antitumor immunity can open new avenues for treatment design. In this review, we discuss the roles of tissue-specific antigen-presenting cells (APCs) in governing antitumor immune responses, with a particular focus on the contributions of tissue-specific dendritic cells. Using the framework of the Cancer-Immunity Cycle, we examine the contributions of tissue-specific APC in CBT-sensitive and CBT-resistant carcinomas, highlight how these cells can be therapeutically modulated, and identify gaps in knowledge that remain to be addressed.

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Unleashing Tumour-Dendritic Cells to Fight Cancer by Tackling Their Three A’s: Abundance, Activation and Antigen-Delivery

Cited by 15 publications

References 108 publications

The Therapeutic Potential of Tackling Tumor-Induced Dendritic Cell Dysfunction in Colorectal Cancer

The Therapeutic Potential of Tackling Tumor-Induced Dendritic Cell Dysfunction in Colorectal Cancer

Theranostics in immuno-oncology using nanobody derivatives

Impact of anatomic site on antigen-presenting cells in cancer

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