Chemokines: A New Dendritic Cell Signal for T Cell Activation

Thaiss, Christoph A.; Semmling, Verena; Franken, Lars; Wagner, Hermann; Kurts, Christian

doi:10.3389/fimmu.2011.00031

Cited by 57 publications

(47 citation statements)

References 78 publications

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“…cDCs, particularly cDCs1, are key cellular sources of T cell-attracting chemokines at tumor sites 10 . Chemokines not only attract T cells at sites of antigen presentation, but also enhance T cell priming by prolonging the contact duration between T cells and DCs 64,65 . In line with this, blocking chemokines in cDC-T cell co-cultures in vitro sufficed to impair T cell priming.…”

Section: Discussionmentioning

confidence: 99%

Wnt1 silences chemokine genes in dendritic cells and induces adaptive immune resistance in lung adenocarcinoma

et al. 2019

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Lung adenocarcinoma (LUAD)-derived Wnts increase cancer cell proliferative/stemness potential, but whether they impact the immune microenvironment is unknown. Here we show that LUAD cells use paracrine Wnt1 signaling to induce immune resistance. In TCGA, Wnt1 correlates strongly with tolerogenic genes. In another LUAD cohort, Wnt1 inversely associates with T cell abundance. Altering Wnt1 expression profoundly affects growth of murine lung adenocarcinomas and this is dependent on conventional dendritic cells (cDCs) and T cells. Mechanistically, Wnt1 leads to transcriptional silencing of CC/CXC chemokines in cDCs, T cell exclusion and cross-tolerance. Wnt-target genes are up-regulated in human intratumoral cDCs and decrease upon silencing Wnt1, accompanied by enhanced T cell cytotoxicity. siWnt1-nanoparticles given as single therapy or part of combinatorial immunotherapies act at both arms of the cancer-immune ecosystem to halt tumor growth. Collectively, our studies show that Wnt1 induces immunologically cold tumors through cDCs and highlight its immunotherapeutic targeting.

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Section: Discussionmentioning

confidence: 99%

Wnt1 silences chemokine genes in dendritic cells and induces adaptive immune resistance in lung adenocarcinoma

et al. 2019

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“…They were found to act as both, stimulators of tumor-development by targeting tumor cells and vascular endothelial cells and thus regulating tumor cell proliferation, cancer invasiveness, and metastasis and antitumorresponse by recruitment of regulatory effector T-cells and antitumor-CTL (Chow and Luster 2014;Nagarsheth et al 2017). Therefore, the presence of chemokines, which determine recruitment of different immune cell subsets is one of the key factors in an efficient antitumorimmune-response (Nagarsheth et al 2017;Thaiss et al 2011).…”

Section: Role Of Chemokines In Tumor Immunology and In Immunotherapymentioning

confidence: 99%

Serum Chemokine-release Profiles in AML-patients Might Contribute to Predict the Clinical Course of the Disease

Merle

Fischbacher

Liepert

et al. 2019

Immunological Investigations

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In cancer or hematologic disorders, chemokines act as growth-or survival factors, regulating hematopoiesis and angiogenesis, determining metastatic spread and controlling leukocyte infiltration into tumors to inhibit antitumor immune responses. The aim was to quantify the release of CXCL8, −9, −10, CCL2, −5, and IL-12 in AML/ MDS-pts' serum by cytometric bead array and to correlate data with clinical subtypes and courses. Minimal differences in serum-levels subdivided into various groups (e.g. age groups, FAB-types, blastproportions, cytogenetic-risk-groups) were seen, but higher release of CXCL8, −9, −10 and lower release of CCL2 and −5 tendentially correlated with more favorable subtypes (<50 years of age, <80% blasts in PB). Comparing different stages of the disease higher CCL5-release in persisting disease and a significantly higher CCL2release at relapse were found compared to first diagnosispointing to a change of 'disease activity' on a chemokine level. Correlations with later on achieved response to immunotherapy and occurrence of GVHD were seen: Higher values of CXCL8, −9, −10 and CCL2 and lower CCL5-values correlated with achieved response to immunotherapy. Predictive cut-off-values were evaluated separating the groups in 'responders' and 'non-responders'. Higher levels of CCL2 and −5 but lower levels of CXCL8, −9, −10 correlated with occurrence of GVHD. We conclude, that in AML-pts' serum higher values of CXCL8, −9, −10 and lower values of CCL5 and in part of CCL2 correlate with more favorable subtypes and improved antitumor'-reactive function. This knowledge can contribute to develop immune-modifying strategies that promote antileukemic adaptive immune responses.

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“…[32][33][34][35][36][37] As adaptive immunity gets triggered, various chemokines such as CXCR3, CXCR4 get secreted after the APCs link to the innate cells to regulate the signaling cascades. 38 The phylogenetic relationship of MHCI, CXCR3 and CXCR4 sequences of C. catla along with sequences of other vertebrates was computed in Mega6.0 software which showed two different clusters involving fish and mammalians. The position of amphibian Xenopus in the phylogenetic tree confirmed the evolutionary link with both the fishes and Streptococcus uberis.…”

Section: Discussionmentioning

confidence: 99%

Molecular cloning, characterization and expression analysis of MHCI and chemokines CXCR3 and CXCR4 gene from freshwater carp,Catla catla

Banerjee

Roy

Samanta

et al. 2019

Microbiology and Immunology

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The immune system with large number of molecules protects the host against a plethora of continuously evolving microbes. Major histocompatibility complex (MHC) molecules serve as cardinal elements of the adaptive immune system responsible for the activation of the adaptive immunity in the host. The present study reports MHCI molecule in freshwater carp, Catla catla, and its differential expression in immunologically relevant tissues post-infection with Gramnegative and Gram-positive bacteria. The MHCI sequence of C. catla had 502 bp nucleotides encoding putative 146 amino acids. The phylogenetic analysis exhibited its evolutionary conservation within the Cyprinidae family and formed a different clade with the higher vertebrates. Simultaneously, CXCR3 and CXCR4 chemokines were cloned and characterized for their expression in infected tissues. Analysis of immunologically relevant tissues of the infected fish exhibited an increase of MHCI gene expression and the down-regulation of CXCR3 and CXCR4 chemokines, indicating a tricky interaction between the innate and adaptive immune system. It was found that intestine, skin and spleen played a crucial role in the contribution of the defense activity which instigated the self-immunity. These immune activities can provide useful information to understand the interaction of self and non-self-immune system in freshwater fish, Catla catla.

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Chemokines: A New Dendritic Cell Signal for T Cell Activation

Cited by 57 publications

References 78 publications

Wnt1 silences chemokine genes in dendritic cells and induces adaptive immune resistance in lung adenocarcinoma

Wnt1 silences chemokine genes in dendritic cells and induces adaptive immune resistance in lung adenocarcinoma

Serum Chemokine-release Profiles in AML-patients Might Contribute to Predict the Clinical Course of the Disease

Molecular cloning, characterization and expression analysis of MHCI and chemokines CXCR3 and CXCR4 gene from freshwater carp,Catla catla

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