Cross-Talks between Natural Killer Cells and Distinct Subsets of Dendritic Cells

Ferlazzo, Guido; Morandi, Barbara

doi:10.3389/fimmu.2014.00159

Cited by 153 publications

(161 citation statements)

References 71 publications

(83 reference statements)

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“…Such "DC-editing" by NK cells occurs both in peripheral tissues and in secondary lymphoid organs (36). This is well in accord with our observations of Ad5/3-D24-tras-treated mice showing redistribution of NK cells toward tumors and draining lymph nodes, coinciding with accumulation of activated DCs and reduction in immature DCs.…”

Section: Discussionsupporting

confidence: 91%

“…Interestingly, NK cell depletion by anti-asialo antibody completely blunted this effect (P ¼ 0.037, as compared with Ad5/3-D24-tras), indicating a central role for NK cells in editing/stimulating DCs, as has been previously suggested (36). A similar trend was observed with regard to CD80-single-positive DCs.…”

Section: Treatment With Trastuzumab-coding Oncolytic Adenovirus Resulsupporting

confidence: 80%

“…S6). In fact, all of these observations are likely to be connected since emerging evidence indicates intimate crosstalk between DCs and NK cells (36).…”

Section: Discussionmentioning

confidence: 98%

“…Matured NK cells also secrete TNFa and IFNg that induce DC maturation and migration, and polarize primed CD4 þ T cells into T-helper 1 (Th1) phenotype, thus promoting cytotoxic T-cell responses (36). Importantly, also oncolytic adenoviruses skew the adaptive immunity toward Th1 phenotype, both preclinically and in cancer patients (17,50), which suggests further combinatorial benefits with trastuzumab.…”

Section: Discussionmentioning

confidence: 99%

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Oncolytic Adenovirus Expressing Monoclonal Antibody Trastuzumab for Treatment of HER2-Positive Cancer

Liikanen

Tähtinen

Guse

et al. 2016

Molecular Cancer Therapeutics

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Monoclonal anti-HER2 antibody trastuzumab has significantly improved the survival of patients with HER2-overexpressing tumors. Nevertheless, systemic antibody therapy is expensive, limited in efficacy due to physical tumor barriers, and carries the risk of severe side effects such as cardiomyopathy. Oncolytic viruses mediate cancer-selective transgene expression, kill infected cancer cells while mounting antitumor immune responses, and have recently demonstrated promising efficacy in combination treatments. Here, we armed an oncolytic adenovirus with fulllength trastuzumab to achieve effective in situ antibody production coupled with progressive oncolytic cancer cell killing. We constructed an infectivity-enhanced serotype 5 oncolytic adenovirus, Ad5/3-D24-tras, coding for human trastuzumab antibody heavy-and light-chain genes, connected by an internal ribosome entry site. Infected cancer cells were able to assemble full-length functional antibody, as confirmed by Western blot, ELISA, and antibody-dependent cell-mediated cytotoxicity assay. Importantly, oncolysis was required for release of the antibody into tumors, providing additional spatial selectivity. Ad5/3-D24-tras showed potent in vitro cytotoxicity and enhanced antitumor efficacy over oncolytic control virus Ad5/3-D24 or commercial trastuzumab in HER2-positive cancer models in vivo (both P < 0.05). Furthermore, Ad5/3-D24-tras resulted in significantly higher tumor-to-systemic antibody concentrations (P < 0.001) over conventional delivery. Immunological analyses revealed dendritic cell activation and natural killer cell accumulation in tumor-draining lymph nodes. Thus, Ad5/3-D24-tras is an attractive anticancer approach combining oncolytic immunotherapy with local trastuzumab production, resulting in improved in vivo efficacy and immune cell activation in HER2-positive cancer. Moreover, the finding that tumor cells can produce functional antibody as directed by oncolytic virus could lead to many valuable antitumor approaches. Mol Cancer Ther; 15(9); 2259-69. Ó2016 AACR.

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Section: Discussionsupporting

confidence: 91%

Section: Treatment With Trastuzumab-coding Oncolytic Adenovirus Resulsupporting

confidence: 80%

“…S6). In fact, all of these observations are likely to be connected since emerging evidence indicates intimate crosstalk between DCs and NK cells (36).…”

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Oncolytic Adenovirus Expressing Monoclonal Antibody Trastuzumab for Treatment of HER2-Positive Cancer

Liikanen

Tähtinen

Guse

et al. 2016

Molecular Cancer Therapeutics

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“…Accordingly, enhanced killing of K562 and lymphoma cells by NK effectors could be demonstrated upon stimulation of lymphocytes with tumor cellloaded IFN-DC. Although the cross-talk between NK cells and mature DC has been largely described (19,20), it should be pointed out that, in contrast to classical monocyte-derived DC, IFN-DC were shown not to need any additional factors to behave like mature DC (7,10) and spontaneously produce chemokines known to promote NK cell recruitment (21). Moreover, differentiation of monocytes into IFN-DC in the presence of NK cells was previously shown to favor a more mature DC phenotype (22).…”

Section: Discussionmentioning

confidence: 99%

NK Cell Activation in the Antitumor Response Induced by IFN-α Dendritic Cells Loaded with Apoptotic Cells from Follicular Lymphoma Patients

Lapenta

Donati

Spadaro

et al. 2016

The Journal of Immunology

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Follicular lymphoma (FL) is the most common form of indolent non-Hodgkin lymphoma. This malignancy is considered virtually incurable, with high response rates to therapy but frequent relapses. We investigated the ability of monocyte-derived dendritic cells generated in the presence of IFN-α and GM-CSF (IFN-DC) and loaded with apoptotic lymphoma cells to activate immune responses against FL cells, with the ultimate goal of designing novel patient-specific vaccination strategies for the treatment of FL. In this article, we show that apoptotic tumor cell–loaded IFN-DC from FL patients, which were cultured for 2 wk with autologous lymphocytes, led to Th1 response skewing, based on significantly higher levels of IFN-γ production and a remarkable increase in CD8+ and NK cell frequency, consistent with the detection of enhanced cytotoxic effector function toward autologous FL cells. IFN-DC were found to promote efficient NK cell activation, increased expression of cytotoxicity receptors, and extensive IFN-γ production in the virtual absence of IL-10. Moreover, direct recognition and killing of primary autologous lymphoma cells by activated NK cells from FL patients was also demonstrated. A critical role was demonstrated for MHC class I–related chain A and B and membrane-bound IL-15 in IFN-DC–mediated NK cell activation and early IFN-γ production. The overall results indicate that IFN-DC loaded with autologous apoptotic FL cells represent a valuable tool for improving the potency of therapeutic cancer vaccines through the efficient induction of NK cell activation and promotion of CD8+ T cell antitumor immunity.

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Immune cell communication in liver disease and liver regeneration

Boghal

Stephenson

Afford

2015

Signaling Pathways in Liver Diseases

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Cross-Talks between Natural Killer Cells and Distinct Subsets of Dendritic Cells

Cited by 153 publications

References 71 publications

Oncolytic Adenovirus Expressing Monoclonal Antibody Trastuzumab for Treatment of HER2-Positive Cancer

Oncolytic Adenovirus Expressing Monoclonal Antibody Trastuzumab for Treatment of HER2-Positive Cancer

NK Cell Activation in the Antitumor Response Induced by IFN-α Dendritic Cells Loaded with Apoptotic Cells from Follicular Lymphoma Patients

Immune cell communication in liver disease and liver regeneration

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