CD137L-stimulated dendritic cells are more potent than conventional dendritic cells at eliciting cytotoxic T-cell responses

Harfuddin, Zulkarnain; Kwajah, Shaqireen; Sim, Adrian Chong Nyi; MacAry, Paul A.; Schwarz, Herbert

doi:10.4161/onci.26859

Cited by 28 publications

(29 citation statements)

References 55 publications

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“…4C). CD137-CD137L (4-1BB-4-1BBL) was also recently implicated in DC-mediated T-cell priming (40,43). We therefore tested whether blocking of CD137L modulates CD4 ϩ T-cell-induced activation of memory CD8 ϩ T cells.…”

Section: Cd40-cd40l Cd80/86-cd28 and Cd137-cd137l Are Not Involved mentioning

confidence: 99%

Cognate CD4 T-Cell Licensing of Dendritic Cells Heralds Anti-Cytomegalovirus CD8 T-Cell Immunity after Human Allogeneic Umbilical Cord Blood Transplantation

Flinsenberg

Spel

Jansen

et al. 2015

J Virol

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Reactivation of human cytomegalovirus (CMV) is hazardous to patients undergoing allogeneic cord blood transplantation (CBT), T-cell-mediated immunity and fight off viral reactivation in CBT patients. IMPORTANCE Survival rates after stem cell transplantation are lowered by 25% when patients undergo reactivation of cytomegalovirus (CMV) that they harbor. Immune protection against CMV is mostly executed by white blood cells called killer T cells. We here show that for generation of optimally protective killer T-cell responses that respond to CMV, the early elicitation of help from a second branch of CMV-directed T cells, called helper T cells, is required.C ytomegalovirus (CMV)-seropositive patients who are immunocompromised are at increased risk for developing potentially life-threatening CMV reactivation. Especially after allogeneic cord blood (CB) transplantation (CBT), the first weeks of immune reconstitution are hazardous for developing CMV reactivation, which is associated with decreased survival rates (1, 2). Antiviral treatment can reduce CMV viremia, but effective viral control requires induction of CMV-directed immunity by T lymphocytes. In particular, CD8 ϩ cytotoxic T lymphocytes (CTLs) fulfill a predominant role in protection against CMV disease (2-4). Therefore, strategies that increase early CMV-specific adaptive immune responses after transplantation are currently being explored, which could ultimately help to establish full clearance of, and long-term immunological memory against, CMV. In the human setting, cell-based therapy is being explored, geared toward dendritic cell (DC)-mediated activation of CTLs (5, 6). The elicitation of antigen-specific CTL immunity was in mouse models shown to require cognate CD4 ϩ T-cell licensing (7-10). Furthermore, priming of naive CD8 ϩ T cells requires both the CD4 ϩ T-helper cells and CD8 ϩ T cells to recognize antigen on the same antigen-presenting cell (5,11,12). Such CD4 ϩ T-cell help can involve CD40 ligand (CD40L) binding to CD40 on DCs (9,13,14). For humans, a requirement for CD4 CMV-specific CD4ϩ T-cell clones are present in the healthy population, suggesting a role for antigen-specific CD4 ϩ T cells in immunity against CMV, as 50 to 80% of adults experience CMV infection in their lifetime (6,15). Moreover, effective control of CMV infection was attained in patients when CMV-specific T cells, of which 77% were CD4 ϩ T cells, were infused (16). Further, human DCs loaded with both HLA class I and II/peptide complexes were more effective at generating antigen-specific CTL responses than were those loaded with solely major histocompatibility complex (MHC) class I/peptide complexes (17). In a different setting, not only the absence of antigen-specific CTLs but also the absence of specific CD4 ϩ T-helper cells resulted in higher

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Section: Cd40-cd40l Cd80/86-cd28 and Cd137-cd137l Are Not Involved mentioning

confidence: 99%

Cognate CD4 T-Cell Licensing of Dendritic Cells Heralds Anti-Cytomegalovirus CD8 T-Cell Immunity after Human Allogeneic Umbilical Cord Blood Transplantation

Flinsenberg

Spel

Jansen

et al. 2015

J Virol

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“…23,24 Recent mouse data demonstrated, however, that maturation of DC solely by pro-inflammatory cytokines yielded DC that failed to efficiently direct effector T cell differentiation. Interestingly, DC matured in the presence of Toll like receptor (TLR) ligands were able to induce full T cell effector function and induce more potent immune responses.…”

Section: Muc1mentioning

confidence: 99%

Dendritic cell immunotherapy in uterine cancer

Coosemans

Tuyaerts

Vanderstraeten

et al. 2014

Human Vaccines & Immunotherapeutics

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“…The rationale behind all these approaches is that DCs become loaded ex vivo with TAAs or TAA-coding molecules, hence becoming able to prime TAA-targeting immune responses upon reinfusion. Additional DC-based anticancer immunotherapies include the targeting of specific TAAs to DCs in vivo [169,[198][199][200][201][202][203][204][205], the use of DC-derived exosomes [206][207][208], and the (re-)administration of autologous or allogeneic DCs amplified, matured and optionally genetically modified ex vivo, but not loaded with TAAs [209][210][211][212][213][214]. In the former setting, TAAs are fused to mAbs, polypeptides or carbohydrates that selectively bind to DCs [169, 198-202, 215, 216], encapsulated in DC-targeting immunoliposomes [217,218], or (3) encoded by DC-specific vectors [219][220][221].…”

Section: Active Immunotherapy Dc-based Immunotherapiesmentioning

confidence: 99%

Untitled

2014

Oncotarget

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During the past decades, anticancer immunotherapy has evolved from a promising therapeutic option to a robust clinical reality. Many immunotherapeutic regimens are now approved by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, and many others are being investigated as standalone therapeutic interventions or combined with conventional treatments in clinical studies. Immunotherapies may be subdivided into "passive" and "active" based on their ability to engage the host immune system against cancer. Since the anticancer activity of most passive immunotherapeutics (including tumor-targeting monoclonal antibodies) also relies on the host immune system, this classification does not properly reflect the complexity of the drug-host-tumor interaction. Alternatively, anticancer immunotherapeutics can be classified according to their antigen specificity. While some immunotherapies specifically target one (or a few) defined tumor-associated antigen(s), others operate in a relatively non-specific manner and boost natural or therapy-elicited anticancer immune responses of unknown and often broad specificity. Here, we propose a critical, integrated classification of anticancer immunotherapies and discuss the clinical relevance of these approaches. www.impactjournals.com/oncotarget 174. Fernandez NC, Lozier A, Flament C, Ricciardi-Castagnoli P, Bellet D, Suter M, Perricaudet M, Tursz T, Maraskovsky E, Zitvogel L. Dendritic cells directly trigger NK cell functions: cross-talk relevant in innate anti-tumor immune responses in vivo. Nat Med. 1999; 5:405-411. 175.

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CD137L-stimulated dendritic cells are more potent than conventional dendritic cells at eliciting cytotoxic T-cell responses

Cited by 28 publications

References 55 publications

Cognate CD4 T-Cell Licensing of Dendritic Cells Heralds Anti-Cytomegalovirus CD8 T-Cell Immunity after Human Allogeneic Umbilical Cord Blood Transplantation

Cognate CD4 T-Cell Licensing of Dendritic Cells Heralds Anti-Cytomegalovirus CD8 T-Cell Immunity after Human Allogeneic Umbilical Cord Blood Transplantation

Dendritic cell immunotherapy in uterine cancer

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