Strategies to overcome DC dysregulation in the tumor microenvironment

Mestrallet, G; Sone, Kazuki; Bhardwaj, Nina

doi:10.3389/fimmu.2022.980709

Cited by 30 publications

(23 citation statements)

References 171 publications

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“…Non-responders patients are characterized by higher infiltration by myeloid subsets, including DC cell resting and macrophages. This is in line with studies showing that immune resistance following ICB may be mediated by myeloid subsets (22)(23)(24). Here, we show that non-responders to ICB are characterized by an increase in immunoregulatory ADORA2A gene expression in CD8+ T cell, M1 and M2 clusters.…”

Section: Discussionsupporting

confidence: 92%

Immune response and resistance of clear cell renal cell carcinoma patients following immune checkpoint blockade

Mestrallet

2023

Preprint

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Abstract175,000 patients die because of renal cell carcinoma (RCC) each year. Clear cell renal cell carcinoma (ccRCC or KIRC) is the most frequent subtype of RCC. Current therapies include immune checkpoint inhibitors (ICB) or VEGFR tyrosine kinase inhibitors (TKIs). However, many patients did not respond to ICB and immune resistance still occurred. Immune resistance may be explained by expression of various immune checkpoints and immunosuppressive pathways in KIRC patients. Thus, it is important to identify mechanisms driving immune response and resistance following ICB. To address this question, we performed an analysis of 3 KIRC cohorts treated with 3 different ICB. Overall, 20-30% of KIRC patients respond to ICB. Responders with metastasized stage IV cancer with tumorectomy prior to anti-PD-L1 are characterized by an increase in CD4+ and CD8+ T cell infiltration, and by better antigen presentation and T cell responses (BTN3A1, PRF1andCD27genes). However, the expression of CTLA4, TIGIT and BTLA in Th1, Th17 and M2 subsets may limit complete response in responders. Importantly, non-responders patients are characterized by higher infiltration by macrophages, and by overexpression of regulatory gene (ADORA2A) in Th2, CD8+ T cell, M1 and M2 clusters. Targeting these pathways may help to develop combination therapies to improve KIRC patient outcomes.

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Section: Discussionsupporting

confidence: 92%

Immune response and resistance of clear cell renal cell carcinoma patients following immune checkpoint blockade

Mestrallet

2023

Preprint

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“…Various immunosuppressive factors are also present in WTLs, which inhibit DC maturation and T cell activation. 30,540 To overcome these issues, extracellular vesicles (EVs) produced by tumor cells have recently been shown to be a vaccination platform that supports DC maturation and neoantigen presentation. Tumor cell-derived EVs can deliver tumor antigen repertoires into DCs and facilitate neoantigen cross-presentation.…”

Section: Determination and Monitoring Of Neoantigen-specific T Cell R...mentioning

confidence: 99%

Neoantigens: promising targets for cancer therapy

Xie

Shen

Gao

et al. 2023

Sig Transduct Target Ther

237

150

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Recent advances in neoantigen research have accelerated the development and regulatory approval of tumor immunotherapies, including cancer vaccines, adoptive cell therapy and antibody-based therapies, especially for solid tumors. Neoantigens are newly formed antigens generated by tumor cells as a result of various tumor-specific alterations, such as genomic mutation, dysregulated RNA splicing, disordered post-translational modification, and integrated viral open reading frames. Neoantigens are recognized as non-self and trigger an immune response that is not subject to central and peripheral tolerance. The quick identification and prediction of tumor-specific neoantigens have been made possible by the advanced development of next-generation sequencing and bioinformatic technologies. Compared to tumor-associated antigens, the highly immunogenic and tumor-specific neoantigens provide emerging targets for personalized cancer immunotherapies, and serve as prospective predictors for tumor survival prognosis and immune checkpoint blockade responses. The development of cancer therapies will be aided by understanding the mechanism underlying neoantigen-induced anti-tumor immune response and by streamlining the process of neoantigen-based immunotherapies. This review provides an overview on the identification and characterization of neoantigens and outlines the clinical applications of prospective immunotherapeutic strategies based on neoantigens. We also explore their current status, inherent challenges, and clinical translation potential.

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“…On the other hand, dendritic cells that have arisen from the myeloid linage are known to be pro-inflammatory and, thus, support antitumor immunity [ 162 ]. Additionally, it has been shown that tumor cells within the brain are capable of inhibiting the maturation of DC [ 163 ]. This prevents them from proper antigen presentation and enhances their immunosuppression activity by inducing the production of Il10 and TGF-β, hence, Treg recruitment [ 164 ].…”

Section: Survival Of Cancer Cells In the Metastatic Environmentmentioning

confidence: 99%

The Journey of Cancer Cells to the Brain: Challenges and Opportunities

Łazarczyk

Mickael

Skiba

et al. 2023

IJMS

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Cancer metastases into the brain constitute one of the most severe, but not uncommon, manifestations of cancer progression. Several factors control how cancer cells interact with the brain to establish metastasis. These factors include mediators of signaling pathways participating in migration, infiltration of the blood–brain barrier, interaction with host cells (e.g., neurons, astrocytes), and the immune system. Development of novel therapies offers a glimpse of hope for increasing the diminutive life expectancy currently forecasted for patients suffering from brain metastasis. However, applying these treatment strategies has not been sufficiently effective. Therefore, there is a need for a better understanding of the metastasis process to uncover novel therapeutic targets. In this review, we follow the journey of various cancer cells from their primary location through the diverse processes that they undergo to colonize the brain. These processes include EMT, intravasation, extravasation, and infiltration of the blood–brain barrier, ending up with colonization and angiogenesis. In each phase, we focus on the pathways engaging molecules that potentially could be drug target candidates.

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Strategies to overcome DC dysregulation in the tumor microenvironment

Cited by 30 publications

References 171 publications

Immune response and resistance of clear cell renal cell carcinoma patients following immune checkpoint blockade

Immune response and resistance of clear cell renal cell carcinoma patients following immune checkpoint blockade

Neoantigens: promising targets for cancer therapy

The Journey of Cancer Cells to the Brain: Challenges and Opportunities

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