scholarly journals Engineering dendritic cell vaccines to improve cancer immunotherapy

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Caleb R. Perez ◽  
Michele De Palma
Keyword(s):  
Cancer Immunotherapy ◽  
Rational Design ◽  
Adaptive Immune System ◽  
Tumour Microenvironment ◽  
Tumour Immunity ◽  
Dendritic Cell Vaccines ◽  
Dc Vaccines ◽  
Personalized Cancer

AbstractAt the interface between the innate and adaptive immune system, dendritic cells (DCs) play key roles in tumour immunity and hold a hitherto unrealized potential for cancer immunotherapy. Here we review the role of distinct DC subsets in the tumour microenvironment, with special emphasis on conventional type 1 DCs. Integrating new knowledge of DC biology and advancements in cell engineering, we provide a blueprint for the rational design of optimized DC vaccines for personalized cancer medicine.

scholarly journals Personalized neoantigen-pulsed dendritic cell vaccines show superior immunogenicity to neoantigen-adjuvant vaccines in mouse tumor models

2019 ◽  
Vol 69 (1) ◽  
pp. 135-145 ◽  
Author(s):  
Rui Zhang ◽  
Fengjiao Yuan ◽  
Yang Shu ◽  
Yaomei Tian ◽  
Bailing Zhou ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Immune Responses ◽  
Cancer Vaccines ◽  
Therapeutic Effects ◽  
Mouse Tumor ◽  
Pulsed Dc ◽  
Dendritic Cell Vaccines ◽  
Dc Vaccines ◽  
T Cell Immune Responses ◽  
Personalized Cancer

AbstractDevelopment of personalized cancer vaccines based on neoantigens has become a new direction in cancer immunotherapy. Two forms of cancer vaccines have been widely studied: tumor-associated antigen (including proteins, peptides, or tumor lysates)-pulsed dendritic cell (DC) vaccines and protein- or peptide-adjuvant vaccines. However, different immune modalities may produce different therapeutic effects and immune responses when the same antigen is used. Therefore, it is necessary to choose a more effective neoantigen vaccination method. In this study, we compared the differences in immune and anti-tumor effects between neoantigen-pulsed DC vaccines and neoantigen-adjuvant vaccines using murine lung carcinoma (LL2) candidate neoantigens. The enzyme-linked immunospot (ELISPOT) assay showed that 4/6 of the neoantigen-adjuvant vaccines and 6/6 of the neoantigen-pulsed DC vaccines induced strong T-cell immune responses. Also, 2/6 of the neoantigen-adjuvant vaccines and 5/6 of the neoantigen-pulsed DC vaccines exhibited potent anti-tumor effects. The results indicated that the neoantigen-pulsed DC vaccines were superior to the neoantigen-adjuvant vaccines in both activating immune responses and inhibiting tumor growth. Our fundings provide an experimental basis for the selection of immune modalities for the use of neoantigens in individualized tumor immunotherapies.

scholarly journals A Forgotten Corner in Cancer Immunotherapy: The Role of Lipids

2021 ◽  
Vol 11 ◽  
Author(s):  
Yang Yu ◽  
Lei Gao ◽  
Yunpeng Wang ◽  
Bo Xu ◽  
Ewetse Paul Maswikiti ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cancer Cells ◽  
Cancer Immunotherapy ◽  
Tumour Microenvironment ◽  
Metabolic Reprogramming ◽  
Great Success ◽  
The Past ◽  
Cancer Immunity ◽  
Molecular Forces

In the past decade, cancer immunotherapy has achieved great success owing to the unravelling of unknown molecular forces in cancer immunity. However, it is critical that we address the limitations of current immunotherapy, including immune-related adverse events and drug resistance, and further enhance current immunotherapy. Lipids are reported to play important roles in modulating immune responses in cancer. Cancer cells use lipids to support their aggressive behaviour and allow immune evasion. Metabolic reprogramming of cancer cells destroys the equilibrium between lipid anabolism and catabolism, resulting in lipid accumulation within the tumour microenvironment (TME). Consequently, ubiquitous lipids, mainly fatty acids, within the TME can impact the function and phenotype of infiltrating immune cells. Determining the complex roles of lipids and their interactions with the TME will provide new insight for improving anti-tumour immune responses by targeting lipids. Herein, we present a review of recent literature that has demonstrated how lipid metabolism reprogramming occurs in cancer cells and influences cancer immunity. We also summarise the potential for lipid-based clinical translation to modify immune treatment.

scholarly journals Combinatorial Immunotherapies for Metastatic Colorectal Cancer

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1875 ◽  
Author(s):  
Eline Janssen ◽  
Beatriz Subtil ◽  
Fàtima de la Jara Ortiz ◽  
Henk M. W. Verheul ◽  
Daniele V. F. Tauriello
Keyword(s):  
Colorectal Cancer ◽  
Rational Design ◽  
Treatment Options ◽  
Tumour Microenvironment ◽  
Preclinical Models ◽  
Major Barrier ◽  
Tumour Immunity ◽  
Cellular Transplantation ◽  
Targeted Treatments ◽  
Key Factor

Colorectal cancer (CRC) is one of the most frequent and deadly forms of cancer. About half of patients are affected by metastasis, with the cancer spreading to e.g., liver, lungs or the peritoneum. The majority of these patients cannot be cured despite steady advances in treatment options. Immunotherapies are currently not widely applicable for this disease, yet show potential in preclinical models and clinical translation. The tumour microenvironment (TME) has emerged as a key factor in CRC metastasis, including by means of immune evasion—forming a major barrier to effective immuno-oncology. Several approaches are in development that aim to overcome the immunosuppressive environment and boost anti-tumour immunity. Among them are vaccination strategies, cellular transplantation therapies, and targeted treatments. Given the complexity of the system, we argue for rational design of combinatorial therapies and consider the implications of precision medicine in this context.

scholarly journals Targeted scavenging of extracellular ROS relieves suppressive immunogenic cell death

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Hongzhang Deng ◽  
Weijing Yang ◽  
Zijian Zhou ◽  
Rui Tian ◽  
Lisen Lin ◽  
...  
Keyword(s):  
Cell Death ◽  
T Lymphocytes ◽  
Cancer Immunotherapy ◽  
Tumour Microenvironment ◽  
Immunogenic Cell Death ◽  
Oxygen Species ◽  
Cancer Model ◽  
Antitumour Effect ◽  
Breast Cancer Model ◽  
Personalized Cancer

Abstract Immunogenic cell death (ICD) and tumour-infiltrating T lymphocytes are severely weakened by elevated reactive oxygen species (ROS) in the tumour microenvironment. It is therefore of critical importance to modulate the level of extracellular ROS for the reversal of immunosuppressive environment. Here, we present a tumour extracellular matrix (ECM) targeting ROS nanoscavenger masked by pH sensitive covalently crosslinked polyethylene glycol. The nanoscavenger anchors on the ECM to sweep away the ROS from tumour microenvironment to relieve the immunosuppressive ICD elicited by specific chemotherapy and prolong the survival of T cells for personalized cancer immunotherapy. In a breast cancer model, elimination of the ROS in tumour microenvironment elicited antitumour immunity and increased infiltration of T lymphocytes, resulting in highly potent antitumour effect. The study highlights a strategy to enhance the efficacy of cancer immunotherapy by scavenging extracellular ROS using advanced nanomaterials.

scholarly journals Emerging roles for the IL-6 family of cytokines in pancreatic cancer

2020 ◽  
Vol 134 (16) ◽  
pp. 2091-2115
Author(s):  
Gemma van Duijneveldt ◽  
Michael D.W. Griffin ◽  
Tracy L. Putoczki
Keyword(s):  
Pancreatic Cancer ◽  
Tumour Microenvironment ◽  
Ductal Adenocarcinoma ◽  
Tumour Immunity ◽  
The Past ◽  
Development Of Resistance ◽  
Cancer Pathogenesis ◽  
Dual Targeting ◽  
Poor Patient

Abstract Pancreatic cancer has one of the poorest prognoses of all malignancies, with little improvement in clinical outcome over the past 40 years. Pancreatic ductal adenocarcinoma is responsible for the vast majority of pancreatic cancer cases, and is characterised by the presence of a dense stroma that impacts therapeutic efficacy and drives pro-tumorigenic programs. More specifically, the inflammatory nature of the tumour microenvironment is thought to underlie the loss of anti-tumour immunity and development of resistance to current treatments. Inflammatory pathways are largely mediated by the expression of, and signalling through, cytokines, chemokines, and other cellular messengers. In recent years, there has been much attention focused on dual targeting of cancer cells and the tumour microenvironment. Here we review our current understanding of the role of IL-6, and the broader IL-6 cytokine family, in pancreatic cancer, including their contribution to pancreatic inflammation and various roles in pancreatic cancer pathogenesis. We also summarise potential opportunities for therapeutic targeting of these pathways as an avenue towards combating poor patient outcomes.

scholarly journals Cancer Extracellular Matrix Proteins Regulate Tumour Immunity

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3331
Author(s):  
Alex Gordon-Weeks ◽  
Arseniy Yuzhalin
Keyword(s):  
Extracellular Matrix ◽  
Immune Function ◽  
Cancer Immunotherapy ◽  
Therapeutic Targets ◽  
Extracellular Matrix Proteins ◽  
Tumour Microenvironment ◽  
Matrix Proteins ◽  
Significant Progress ◽  
Tumour Immunity ◽  
Made In

The extracellular matrix (ECM) plays an increasingly recognised role in the development and progression of cancer. Whilst significant progress has been made in targeting aspects of the tumour microenvironment such as tumour immunity and angiogenesis, there are no therapies that address the cancer ECM. Importantly, immune function relies heavily on the structure, physics and composition of the ECM, indicating that cancer ECM and immunity are mechanistically inseparable. In this review we highlight mechanisms by which the ECM shapes tumour immunity, identifying potential therapeutic targets within the ECM. These data indicate that to fully realise the potential of cancer immunotherapy, the cancer ECM requires simultaneous consideration.

scholarly journals A review of cancer immunotherapy: from the past, to the present, to the future

2019 ◽  
Vol 27 (S2) ◽  
Author(s):  
K. Esfahani ◽  
L. Roudaia ◽  
N. Buhlaiga ◽  
S.V. Del Rincon ◽  
N. Papneja ◽  
...  
Keyword(s):  
Cancer Immunotherapy ◽  
Cancer Vaccines ◽  
Standard Of Care ◽  
Tumour Microenvironment ◽  
Standards Of Care ◽  
The Past ◽  
History Of ◽  
Cancer Types ◽  
Personalized Cancer

Compared with previous standards of care (including chemotherapy, radiotherapy, and surgery), cancer immunotherapy has brought significant improvements for patients in terms of survival and quality of life. Immunotherapy has now firmly established itself as a novel pillar of cancer care, from the metastatic stage to the adjuvant and neoadjuvant settings in numerous cancer types. In this review article, we highlight how the history of cancer immunotherapy paved the way for discoveries that are now part of the standard of care. We also highlight the current pitfalls and limitations of cancer checkpoint immunotherapy and how novel research in the fields of personalized cancer vaccines, autoimmunity, the microbiome, the tumour microenvironment, and metabolomics is aiming to solve those challenges.

scholarly journals Dendritic Cell Vaccines for Cancer Immunotherapy: The Role of Human Conventional Type 1 Dendritic Cells

Pharmaceutics ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 158 ◽  
Author(s):  
João Calmeiro ◽  
Mylène A. Carrascal ◽  
Adriana Ramos Tavares ◽  
Daniel Alexandre Ferreira ◽  
Célia Gomes ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Dendritic Cell ◽  
Cancer Immunotherapy ◽  
Natural Killer ◽  
Ex Vivo ◽  
Great Effort ◽  
Tumor Vaccines ◽  
Conventional Type

Throughout the last decades, dendritic cell (DC)-based anti-tumor vaccines have proven to be a safe therapeutic approach, although with inconsistent clinical results. The functional limitations of ex vivo monocyte-derived dendritic cells (MoDCs) commonly used in these therapies are one of the pointed explanations for their lack of robustness. Therefore, a great effort has been made to identify DC subsets with superior features for the establishment of effective anti-tumor responses and to apply them in therapeutic approaches. Among characterized human DC subpopulations, conventional type 1 DCs (cDC1) have emerged as a highly desirable tool for empowering anti-tumor immunity. This DC subset excels in its capacity to prime antigen-specific cytotoxic T cells and to activate natural killer (NK) and natural killer T (NKT) cells, which are critical factors for an effective anti-tumor immune response. Here, we sought to revise the immunobiology of cDC1 from their ontogeny to their development, regulation and heterogeneity. We also address the role of this functionally thrilling DC subset in anti-tumor immune responses and the most recent efforts to apply it in cancer immunotherapy.

scholarly journals IL-6 Activities in the Tumour Microenvironment. Part 1

2019 ◽  
Vol 7 (14) ◽  
pp. 2391-2398 ◽  
Author(s):  
Dimitur Chavdarov Chonov ◽  
Maria Magdalena Krasimirova Ignatova ◽  
Julian Rumenov Ananiev ◽  
Maya Vladova Gulubova
Keyword(s):  
Target Genes ◽  
Elevated Serum ◽  
Serum Levels ◽  
Tumour Microenvironment ◽  
High Endothelial Venules ◽  
Tumour Immunity ◽  
Membrane Bound ◽  
In Trans ◽  
Transcription 3

The predominant role of IL-6 in cancer is its key promotion of tumour growth. IL-6 binds IL-6 receptor (IL-6R) and the membrane-bound glycoprotein gp130. The complex I-6/IL-6R/gp130 starts the Janus kinases (JAKs) and signal transducer and activator of transcription 3 (STAT3) or JAK/STAT3 pathway. IL-6R exits in two forms: a membrane-bound IL-6Rα subunit (mIL-6R) that participates in classic signalling pathway and soluble IL-6R subunit (sIL-6R) engaged in trans-signalling. The pro-tumour functions of IL-6 are associated with STAT3, a major oncogenic transcription factor that triggers up-regulation of target genes responsible for tumour cell survival. IL-6 combined with TGF-β induces proliferation of pathogenic Th17 cells. The anti-tumour function of IL-6 is the promotion of anti-tumour immunity. IL-6 trans-signaling contributed to transmigration of lymphocytes in high endothelial venules (HEV). Dendritic cell (DC) secreted IL-6 in the lymph node influences the activation, distribution and polarisation of the immune response. Elevated serum levels of IL-6 and increased expression of IL-6 in tumour tissue are negative prognostic marker for patients’ survival.

scholarly journals The role of the tumour microenvironment in immunotherapy

2017 ◽  
Vol 24 (12) ◽  
pp. T283-T295 ◽  
Author(s):  
Stephan Gasser ◽  
Lina H K Lim ◽  
Florence S G Cheung
Keyword(s):  
Current Knowledge ◽  
Tumour Progression ◽  
Tumour Microenvironment ◽  
Tumour Immunity ◽  
Recent Success ◽  
Cytokines And Chemokines ◽  
Solid Malignancies ◽  
Variable Success ◽  
Molecular Patterns

Recent success in immunomodulating strategies in lung cancer and melanoma has prompted much enthusiasm in their potential to treat other advanced solid malignancies. However, their applications have shown variable success and are even ineffective against some tumours. The efficiency of immunotherapies relies on an immunogenic tumour microenvironment. The current field of cancer immunology has focused on understanding the interaction of cancer and host immune cells to break the state of immune tolerance and explain how molecular patterns of cytokines and chemokines affect tumour progression. Here, we review our current knowledge of how inherent properties of tumours and their different tumour microenvironments affect therapeutic outcome. We also discuss insights into recent multimodal therapeutic approaches that target tumour immune evasion and suppression to restore anti-tumour immunity.

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