Type I Interferons and Natural Killer Cell Regulation in Cancer

Müller, Lena; Aigner, Petra; Stoiber, Dagmar

doi:10.3389/fimmu.2017.00304

Cited by 118 publications

(104 citation statements)

References 130 publications

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“…Since antigen escape into the cytosol is a rate‐limiting step during the process, the introduction of PC7A, which is capable of enhancing endosomal escape in an acidic environment, enables more efficient MHC I presentation to CD8 + T cells . As reported previously, PC7A can activate the “stimulator of interferon genes” (STING) pathway, thereby increasing DC maturation and proliferation for both NK cells and T cells …”

mentioning

confidence: 83%

Development of an In Situ Cancer Vaccine via Combinational Radiation and Bacterial‐Membrane‐Coated Nanoparticles

et al. 2019

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Neoantigens induced by random mutations and specific to an individual's cancer are the most important tumor antigens recognized by T cells. Among immunologically “cold” tumors, limited recognition of tumor neoantigens results in the absence of a de novo antitumor immune response. These “cold” tumors present a clinical challenge as they are poorly responsive to most immunotherapies, including immune checkpoint inhibitors (ICIs). Radiation therapy (RT) can enhance immune recognition of “cold” tumors, resulting in a more diversified antitumor T‐cell response, yet RT alone rarely results in a systemic antitumor immune response. Therefore, a multifunctional bacterial membrane‐coated nanoparticle (BNP) composed of an immune activating PC7A/CpG polyplex core coated with bacterial membrane and imide groups to enhance antigen retrieval is developed. This BNP can capture cancer neoantigens following RT, enhance their uptake in dendritic cells (DCs), and facilitate their cross presentation to stimulate an antitumor T‐cell response. In mice bearing syngeneic melanoma or neuroblastoma, treatment with BNP+RT results in activation of DCs and effector T cells, marked tumor regression, and tumor‐specific antitumor immune memory. This BNP facilitates in situ immune recognition of a radiated tumor, enabling a novel personalized approach to cancer immunotherapy using off‐the‐shelf therapeutics.

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confidence: 83%

Development of an In Situ Cancer Vaccine via Combinational Radiation and Bacterial‐Membrane‐Coated Nanoparticles

et al. 2019

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“…In this context, Katlinskaya and colleagues have shown that the production of IFN‐β by senescent cells contributes to the NK cell‐mediated clearance of senescent cells not only acting on the effector cells, performing NK cells priming, but also having effect on target senescent cells. Indeed, the engagement of the IFN pathway on senescent cells increases their expression of NKG2D ligands, that is, MICA and ULBP2, promoting NK‐mediated killing .…”

Section: Type I Interferons At the Crossroad Between Senescent And Vimentioning

confidence: 99%

Senescent cells: Living or dying is a matter of NK cells

Antonangeli

Zingoni

Soriani

et al. 2019

Journal of Leukocyte Biology

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NK cells are lymphocytes of the innate immune system, which are able to deal promptly with stressed cells. Cellular senescence is a cell stress response leading to cell cycle arrest that plays a key role during tissue homeostasis and carcinogenesis. In this review, how senescent cells trigger an immune response and, in particular, the ability of NK cells to recognize and clear senescent cells are discussed. Special attention is given to the NK cell‐mediated clearance of senescent tumor cells. NK cells kill senescent cells through a mechanism involving perforin‐ and granzyme‐containing granule exocytosis, and produce IFN‐γ following senescent cell interaction, leading to hypothesize that NK cell‐mediated immune clearance of senescent cells not only relies on direct killing but also on cytokine production, that in turn can promote macrophage activation. These aspects, as well as the ability of the senescence‐associated secretory phenotype and senescent cell‐produced extracellular vesicles to modulate NK cell effector functions, are described.

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“…Independently of the cancer type, we found that 79 (6%) TADs were significantly enriched, with folddifferences of up to 3; in addition, the aforementioned five TADs overlapping with no CNVs were also significantly depleted, with their expectation ranging from 230 to 295 patients (see Materials and Methods and Figure 2B). Compared to other TADs, significantly enriched TADs were mainly associated with type I interferon response and natural killer cell activation (see Supplementary Table S4), which are known to be crucial for efficient tumor immune surveillance (e.g., (39)); depleted TADs were linked to transcriptional regulation. In addition, TADs enriched for CNV tended to be located towards the ends of the chromosomes, reflecting the genomic distribution of CNVs (40).…”

Section: % Of Consensus Tads Are Enriched or Depleted For Cancer-relmentioning

confidence: 99%

The presence of copy number variants in specific topologically associating domains has prognostic value in many cancer types

Nkh

Pilarsky

et al. 2019

Preprint

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The human genome is organized into topologically associating domains (TADs), which represent contiguous regions with a higher frequency of intra-interactions as opposed to inter-interactions. TADs contribute to gene expression regulation by restricting interactions between regulatory elements, and their disruption by genomic rearrangements can result in altered gene expression and, ultimately, in cancer. Here, we provide a proof-of-principle that mutations within TADs can be used to predict the survival of cancer patients. For this purpose, we first constructed a set of 1,467 TADs representing the three-dimensional organization of genome across 24 normal human tissues. We then used Cox regression analysis to assess the prognostic value of the TADs in different cancer types, and identified a total of 35 TADs that were prognostic for at least one of nine cancer types. Interestingly, only 46% of the prognostic TADs comprised one or more genes with a known causal association with cancer. Moreover, for those TADs encompassing such a gene, the prognostic effect of the TAD was only directed related to the presence/absence of mutations in the gene in 13% of the cases. These observations indicate that the predictive power of a large proportion of the prognostic TADs is independent of whether pan-cancer genes are mutated or not.Furthermore, 34% of the 35 prognostic TADs showed strong structural perturbations in the cancer genome, which might mediate cancer development and progression. This study has important implications for the interpretation of cancer-related non-coding mutations and offer insights to new strategies for personalizing cancer medicine.

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Type I Interferons and Natural Killer Cell Regulation in Cancer

Cited by 118 publications

References 130 publications

Development of an In Situ Cancer Vaccine via Combinational Radiation and Bacterial‐Membrane‐Coated Nanoparticles

Development of an In Situ Cancer Vaccine via Combinational Radiation and Bacterial‐Membrane‐Coated Nanoparticles

Senescent cells: Living or dying is a matter of NK cells

The presence of copy number variants in specific topologically associating domains has prognostic value in many cancer types

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