The Varieties of Immunological Experience: Of Pathogens, Stress, and Dendritic Cells

Pulendran, Bali

doi:10.1146/annurev-immunol-020711-075049

Cited by 100 publications

(100 citation statements)

References 320 publications

(387 reference statements)

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“…DCs express numerous pattern recognition receptors, including lectins, Toll-like receptors (TLRs), NOD-like receptors (NLRs) and helicases, through which they can sense microbes and tissue damage (cancer) such as increased pericellular nucleic acids (Pulendran, 2015). If DCs do not receive maturation signals, such as when exposed to high levels of IL-10 (Ruffell et al, 2014), they remain immature and antigen presentation instead leads to T cell suppression.…”

Section: The Makings Of the Immune Response To Cancermentioning

confidence: 99%

The Basis of Oncoimmunology

Palucka

Coussens

2016

Cell

700

554

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Cancer heterogeneity, which enables clonal survival and treatment resistance, is shaped by active immune responses. Antigen-specific T cells can control cancer, as revealed clinically by immunotherapeutics such as adoptive T–cell transfer and checkpoint blockade. The host immune system is thus a powerful tool that if better harnessed could significantly enhance the efficacy of chemotherapeutics and improve outcomes for cancer sufferers. To realize this vision, however, a number of research frontiers must be tackled. These include developing strategies for neutralizing tumor-promoting inflammation, broadening T cell repertoires (via vaccination), and elucidating the mechanisms by which immune cells organize tumor microenvironments to regulate T cell activity. Such efforts will pave the way for identifying new targets for combination therapies that overcome resistance to current treatments and promote long-term cancer control.

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Section: The Makings Of the Immune Response To Cancermentioning

confidence: 99%

The Basis of Oncoimmunology

Palucka

Coussens

2016

Cell

700

554

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“…These parameters relate to T-cell priming and activation. Failure to sustain these hallmarks will lead to tolerogenic DCs that will dampen antitumor immunity (14,15).…”

Section: Introductionmentioning

confidence: 99%

TK Inhibitor Pazopanib Primes DCs by Downregulation of the β-Catenin Pathway

Zizzari

Napoletano

Botticelli

et al. 2018

Cancer Immunology Research

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Tyrosine kinase inhibitors (TKIs) target angiogenesis by affecting, for example, the VEGF receptors in tumors and have improved outcomes for patients with metastatic renal cell carcinoma (mRCC). Immune checkpoint inhibitors (ICIs) have also been proposed for treatment of mRCC with encouraging results. A better understanding of the activity of immune cells in mRCC, the immunomodulatory effects of TKIs, and the characteristics defining patients most likely to benefit from various therapies will help optimize immunotherapeutic approaches. In this study, we investigated the influence of the TKI pazopanib on dendritic cell (DC) performance and immune priming. Pazopanib improved DC differentiation and performance by promoting upregulation of the maturation markers HLA-DR, CD40, and CCR7; decreasing IL10 production and endocytosis; and increasing T-cell proliferation. PD-L1 expression was also downregulated. Our results demonstrate that pazopanib inhibits the Erk/b-catenin pathway, suggesting this pathway might be involved in increased DC activation. Similar results were confirmed in DCs differentiated from mRCC patients during pazopanib treatment. In treated patients pazopanib appeared to enhance a circulating CD4 þ T-cell population that expresses CD137 (4-1BB). These results suggest that a potentially exploitable immunomodulatory effect induced by pazopanib could improve responses of patients with mRCC in customized protocols combining TKIs with ICI immunotherapy. Cancer Immunol Res; 6(6); 711-22. Ó2018 AACR.

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“…Emerging evidence demonstrates that immune cells also sense environmental perturbations that induce cellular stress and metabolic changes (1, 2). However, the mechanisms underlying such environmental sensing are poorly understood.…”

mentioning

confidence: 99%

mTOR regulates metabolic adaptation of APCs in the lung and controls the outcome of allergic inflammation

Sinclair

Bommakanti

Gardinassi

et al. 2017

Science

Self Cite

100

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Antigen-presenting cells (APCs) occupy diverse anatomical tissues, but their tissue-restricted homeostasis remains poorly understood. Here, working in mouse models of inflammation, we found that mTOR-dependent metabolic adaptation was required at discrete locations. mTOR was dispensable for DC homeostasis in secondary lymphoid tissues but necessary to regulate cellular metabolism and accumulation of CD103+ DCs and alveolar macrophages in lung. Moreover, while numbers of mTOR-deficient lung CD11b+ DCs were not changed, they were metabolically reprogrammed to skew allergic inflammation from eosinophilic Th2 to neutrophilic Th17 polarity. The mechanism for this change was independent of translational control but dependent on inflammatory DC, which produced IL-23 and increased fatty acid oxidation. mTOR therefore mediates metabolic adaptation of APCs in distinct tissues, influencing the immunological character of allergic inflammation.

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The Varieties of Immunological Experience: Of Pathogens, Stress, and Dendritic Cells

Cited by 100 publications

References 320 publications

The Basis of Oncoimmunology

The Basis of Oncoimmunology

TK Inhibitor Pazopanib Primes DCs by Downregulation of the β-Catenin Pathway

mTOR regulates metabolic adaptation of APCs in the lung and controls the outcome of allergic inflammation

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