Insights Into Dendritic Cells in Cancer Immunotherapy: From Bench to Clinical Applications.
Ontology highlight
ABSTRACT:
SUBMITTER: Salah A
PROVIDER: S-EPMC8273339 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:PURPOSE:This study aimed to systematically evaluate the efficacy and safety of dendritic cells-cytokine-induced killer (DC-CIK) cells immunotherapy in treating pancreatic cancer (PC) patients. METHODS:Data were collected from published articles of clinical trials. Databases including Web of Science, EMBASE, PubMed, Cochrane Library, Wanfang, and CNKI were searched. The main outcome measures in this research included the overall response rate (ORR), disease control rate (DCR), overall survival (OS), patients' quality of life (QoL), immune function, and adverse events. Comparative analysis was conducted between DC-CIK immunotherapy and chemotherapy (combined therapy) and chemotherapy alone. RESULTS:This analysis covered 14 trials with 1,088 PC patients involved. The combined therapy showed advantages over chemotherapy alone in ORR (odds ratio [OR] =1.69, 95% confidence interval [CI] =1.20-2.38, P=0.003), DCR (OR =2.33, 95% CI =1.63-3.33, P<0.00001), OS (1-year OS, OR =3.61, 95% CI =2.41-5.40, P<0.00001; 3-year OS, OR =2.65, 95% CI =1.56-4.50, P=0.0003) and patients' QoL (P<0.01) with statistical significance. After immunotherapy, lymphocyte subsets' percentages of CD3+ (P<0.00001), CD4+ (P=0.01), CD3+CD56+ (P<0.00001), and cytokine levels of IFN-? (P<0.00001) were significantly increased, and the percentages of CD4+CD25+CD127low (P<0.00001) and levels of IL-4 (P<0.0001) were significantly decreased, whereas analysis on CD8+ (P=0.59) and CD4+/CD8+ ratio (P=0.64) did not show a significant difference. CONCLUSION:The combination of DC-CIK immunotherapy and chemotherapy is effective for PC treatment, indicated by prolonging the PC patients' survival time, which benefit from reconstructed immune function of patients.
| S-EPMC5574601 | biostudies-literature
Project description:Natural killer (NK) cells are unique innate immune cells and manifest rapid and potent cytotoxicity for cancer immunotherapy and pathogen removal without the requirement of prior sensitization or recognition of peptide antigens. Distinguish from the T lymphocyte-based cythotherapy with toxic side effects, chimeric antigen receptor-transduced NK (CAR-NK) cells are adequate to simultaneously improve efficacy and control adverse effects including acute cytokine release syndrome (CRS), neurotoxicity and graft-versus-host disease (GVHD). Moreover, considering the inherent properties of NK cells, the CAR-NK cells are "off-the-shelf" product satisfying the clinical demand for large-scale manufacture for cancer immunotherapy attribute to the cytotoxic effect via both NK cell receptor-dependent and CAR-dependent signaling cascades. In this review, we mainly focus on the latest updates of CAR-NK cell-based tactics, together with the opportunities and challenges for cancer immunotherapies, which represent the paradigm for boosting the immune system to enhance antitumor responses and ultimately eliminate malignancies. Collectively, we summarize and highlight the auspicious improvement in CAR-NK cells and will benefit the large-scale preclinical and clinical investigations in adoptive immunotherapy.
| S-EPMC8932134 | biostudies-literature
Project description:Dendritic cells (DC) are professional antigen presenting cells, uniquely able to induce naïve T cell activation and effector differentiation. They are, likewise, involved in the induction and maintenance of immune tolerance in homeostatic conditions. Their phenotypic and functional heterogeneity points to their great plasticity and ability to modulate, according to their microenvironment, the acquired immune response and, at the same time, makes their precise classification complex and frequently subject to reviews and improvement. This review will present general aspects of the DC physiology and classification and will address their potential and actual uses in the management of human disease, more specifically cancer, as therapeutic and monitoring tools. New combination treatments with the participation of DC will be also discussed.
| S-EPMC6348254 | biostudies-literature
Project description:Dendritic cells (DCs) can initiate and direct adaptive immune responses. This ability is exploitable in DC vaccination strategies, in which DCs are educated ex vivo to present tumor antigens and are administered into the patient with the aim to induce a tumor-specific immune response. DC vaccination remains a promising approach with the potential to further improve cancer immunotherapy with little or no evidence of treatment-limiting toxicity. However, evidence for objective clinical antitumor activity of DC vaccination is currently limited, hampering the clinical implementation. One possible explanation for this is that the most commonly used monocyte-derived DCs may not be the best source for DC-based immunotherapy. The novel approach to use naturally circulating DCs may be an attractive alternative. In contrast to monocyte-derived DCs, naturally circulating DCs are relatively scarce but do not require extensive culture periods. Thereby, their functional capabilities are preserved, the reproducibility of clinical applications is increased, and the cells are not dysfunctional before injection. In human blood, at least three DC subsets can be distinguished, plasmacytoid DCs, CD141+ and CD1c+ myeloid/conventional DCs, each with distinct functional characteristics. In completed clinical trials, either CD1c+ myeloid DCs or plasmacytoid DCs were administered and showed encouraging immunological and clinical outcomes. Currently, also the combination of CD1c+ myeloid and plasmacytoid DCs as well as the intratumoral use of CD1c+ myeloid DCs is under investigation in the clinic. Isolation and culture strategies for CD141+ myeloid DCs are being developed. Here, we summarize and discuss recent clinical developments and future prospects of natural DC-based immunotherapy.
| S-EPMC6471787 | biostudies-literature
Project description:Cancer metastasis is the leading cause of cancer-related death. Circulating tumor cells (CTCs) are shed into the bloodstream from either primary or metastatic tumors during an intermediate stage of metastasis. In recent years, immunotherapy has also become an important focus of cancer research. Thus, to study the relationship between CTCs and immunotherapy is extremely necessary and valuable to improve the treatment of cancer. In this review, based on the advancements of CTC isolation technologies, we mainly discuss the clinical applications of CTCs in cancer immunotherapy and the related immune mechanisms of CTC formation. In order to fully understand CTC formation, sufficiently and completely understood molecular mechanism based on the different immune cells is critical. This understanding is a promising avenue for the development of effective immunotherapeutic strategies targeting CTCs.
| S-EPMC6982393 | biostudies-literature
Project description:Dendritic cells (DCs) are immune specialized cells playing a critical role in promoting immune response against antigens, and may represent important targets for therapeutic interventions in cancer. DCs can be stimulated ex vivo with pro-inflammatory molecules and loaded with tumor-specific antigen(s). Protocols describing the specific details of DCs vaccination manufacturing vary widely, but regardless of the employed protocol, the DCs vaccination safety and its ability to induce antitumor responses is clearly established. Many years of studies have focused on the ability of DCs to provide overall survival benefits at least for a selection of cancer patients. Lessons learned from early trials lead to the hypothesis that, to improve the efficacy of DCs-based immunotherapy, this should be combined with other treatments. Thus, the vaccine's ultimate role may lie in the combinatorial approaches of DCs-based immunotherapy with chemotherapy and radiotherapy, more than in monotherapy. In this review, we address some key questions regarding the integration of DCs vaccination with multimodality therapy approaches for cancer treatment paradigms.
| S-EPMC8620771 | biostudies-literature
Project description:Targeted therapy and immunotherapy in combination is considered the ideal strategy for treating metastatic cancer, as it can eliminate the primary tumors and induce host immunity to control distant metastases. Phototherapy, a promising targeted therapy, eradicates primary tumors using an appropriate dosage of focal light irradiation, while initiating antitumor immune responses through induced immunogenic tumor cell death. Recently, phototherapy has been employed to improve the efficacy of immunotherapies such as chimeric antigen receptor T-cell therapy and immune checkpoint inhibitors. Phototherapy and immunoadjuvant therapy have been used in combination clinically, wherein the induced immunogenic cell death and enhanced antigen presentation synergy, inducing a systemic antitumor immune response to control residual tumor cells at the treatment site and distant metastases. This review summarizes studies on photo-immunotherapy, the combination of phototherapy and immunotherapy, especially focusing on the development and progress of this unique combination from a benchtop project to a promising clinical therapy for metastatic cancer.
| S-EPMC7797676 | biostudies-literature
Project description:Programmed death ligand 1 (PD-L1) has emerged as a biomarker that can help to predict responses to immunotherapies targeted against PD-L1 and its receptor (PD-1). Companion tests for evaluating PD-L1 expression as a biomarker of response have been developed for many cancer immunotherapy agents. These assays use a variety of detection platforms at different levels (protein, mRNA), employ diverse biopsy and surgical samples, and have disparate positivity cutoff points and scoring systems, all of which complicate the standardization of clinical decision-making. This review summarizes the current understanding and ongoing investigations regarding PD-L1 expression as a potential biomarker for clinical outcomes of anti-PD-1/PD-L1 immunotherapy.
| S-EPMC5436438 | biostudies-literature
Project description:Dendritic cells (DCs) are specialized immunostimulatory cells involved in the induction and regulation of immune responses. The feasibility of large-scale ex vivo generation of DCs from patients' monocytes allows for therapeutic application of ex vivo-cultured DCs to bypass the dysfunction of endogenous DCs, restore immune surveillance, induce cancer regression or stabilization or delay or prevent its recurrence. While the most common paradigm of the therapeutic application of DCs reflects their use as cancer 'vaccines', additional and potentially more effective possibilities include the use of patients' autologous DCs as parts of more comprehensive therapies involving in vivo or ex vivo induction of tumor-reactive T cells and the measures to counteract systemic and local immunosuppression in tumor-bearing hosts. Ex vivo-cultured DCs can be instructed to acquire distinct functions relevant for the induction of effective cancer immunity (DC polarization), such as the induction of different effector functions or different homing properties of tumor-specific T cells (delivery of 'signal 3' and 'signal 4'). These considerations highlight the importance of the application of optimized conditions for the ex vivo culture of DCs and the potential combination of DC therapies with additional immune interventions to facilitate the entry of DC-induced T cells to tumor tissues and their local antitumor functions.
| S-EPMC6542562 | biostudies-literature
Project description:Dendritic cells (DCs) are the most powerful immunostimulatory cells specialized in the induction and regulation of immune responses. Their properties and the feasibility of their large-scale ex vivo generation led to the application of ex vivo-educated DCs to bypass the dysfunction of endogenous DCs in cancer patients and to induce therapeutic anti-cancer immunity. While multiple paradigms of therapeutic application of DCs reflect their consideration as cancer "vaccines", numerous features of DC-based vaccination resemble those of autologous transplants, resulting in challenges and opportunities that distinguish them from classical vaccines. In addition to the functional heterogeneity of DC subsets and plasticity of the individual DC types, the unique features of DCs are the kinetic character of their function, limited functional stability, and the possibility to imprint in maturing DCs distinct functions relevant for the induction of effective cancer immunity, such as the induction of different effector functions or different homing properties of tumor-specific T cells (delivery of "signal 3" and "signal 4"). These considerations highlight the importance of the application of optimized, potentially patient-specific conditions of ex vivo culture of DCs and their delivery, with the logistic and regulatory implications shared with transplantation and other surgical procedures.
| S-EPMC3695396 | biostudies-literature