Cytotoxic Chemotherapy as an Immune Stimulus: A Molecular Perspective on Turning Up the Immunological Heat on Cancer.

Abstract:

:Cytotoxic chemotherapeutics (CCTs) are widely used in the treatment of cancer. Although their mechanisms of action have been best understood in terms of targeting the apparatus of mitosis, an ability to stimulate anti-tumor immune responses is increasing the recognition of these agents as immunotherapies. Immune checkpoint blockade antibodies neutralize important, but specific, immune-regulatory interactions such as PD-1/PD-L1 and CTLA-4 to improve the anti-tumor immune response. However, CCTs can provide a broad-acting immune-stimulus against cancer, promoting both T-cell priming and recruitment to the tumor, which compliments the effects of immune checkpoint blockade. A key pathway in this process is "immunogenic cell death" (ICD) which occurs as a result of tumor cell endoplasmic reticulum stress and apoptosis elicited by CCTs. ICD involves a series of non-redundant signaling events which break tolerance and license anti-tumor antigen-specific T-cells, allowing CCTs to act as "in situ" tumor vaccination tools. Not all responses are tumor cell-intrinsic, as CCTs can also modulate the broader tumor microenvironment. This modulation occurs through preferential depletion of stromal cells which suppress and neutralize robust anti-tumor immune responses, such as myeloid cell populations and Tregs, while effector CD8+ and CD4+ T-cells and NK cells are relatively spared. The immune-stimulating effects of CCTs are dependent on chemotherapy class, dose and tumor cell sensitivity to the agent, highlighting the need to understand the underlying biology of these responses. This mini review considers the immune-stimulating effects of CCTs from a molecular perspective, specifically highlighting considerations for their utilization in the context of combinations with immunotherapy.

journal_name

Front Immunol

journal_title

Frontiers in immunology

authors

Opzoomer JW,Sosnowska D,Anstee JE,Spicer JF,Arnold JN

doi

10.3389/fimmu.2019.01654

subject

Has Abstract

pub_date

2019-07-17 00:00:00

pages

1654

issn

1664-3224

journal_volume

10

pub_type

杂志文章,评审
  • Low-Dose Total Body Irradiation Can Enhance Systemic Immune Related Response Induced by Hypo-Fractionated Radiation.

    abstract::A systemic immune related response (SIME) of radiotherapy has been occasionally observed on metastatic tumors, but the clinical outcomes remain poor. Novel treatment approaches are therefore needed to improve SIME ratio. We used a combination of hypo-fractionated radiation therapy (H-RT) with low-dose total body irrad...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.00317

    authors: Liu J,Zhou J,Wu M,Hu C,Yang J,Li D,Wu P,Chen Y,Chen P,Lin S,Cui Y,Fu S,Wu J

    更新日期:2019-02-27 00:00:00

  • Role of SLC7A5 in Metabolic Reprogramming of Human Monocyte/Macrophage Immune Responses.

    abstract::Amino acids (AAs) are necessary nutrients which act not only as building blocks in protein synthesis but also in crucial anabolic cellular signaling pathways. It has been demonstrated that SLC7A5 is a critical transporter that mediates uptake of several essential amino acids in highly proliferative tumors and activate...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.00053

    authors: Yoon BR,Oh YJ,Kang SW,Lee EB,Lee WW

    更新日期:2018-01-25 00:00:00

  • H7N9 Avian Influenza Virus Is Efficiently Transmissible and Induces an Antibody Response in Chickens.

    abstract::H7N9 viruses pose a threat to human health and they are no less harmful to the poultry industry than the H5N1 avian influenza viruses. However, the pathogenesis, transmissibility, and the host immune response of the H7N9 virus in chickens and mice remain unclear. In this study, we found that H7N9 viruses replicated in...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.00789

    authors: Jiao P,Song Y,Huang J,Xiang C,Cui J,Wu S,Qu N,Wang N,Ouyang G,Liao M

    更新日期:2018-04-13 00:00:00

  • Late-Onset Antibody Deficiency Due to Monoallelic Alterations in NFKB1.

    abstract::Adult-onset primary immunodeficiency is characterized by recurrent infections, hypogammaglobulinemia, and poor antibody response to vaccines. In this study, we have analyzed targeted gene panel sequencing results of 270 patients diagnosed with antibody deficiency and identified five disease-associated variants in NFKB...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.02618

    authors: Schröder C,Sogkas G,Fliegauf M,Dörk T,Liu D,Hanitsch LG,Steiner S,Scheibenbogen C,Jacobs R,Grimbacher B,Schmidt RE,Atschekzei F

    更新日期:2019-11-14 00:00:00

  • Recent Progress toward Engineering HIV-1-Specific Neutralizing Monoclonal Antibodies.

    abstract::The recent discoveries of broadly potent neutralizing human monoclonal antibodies represent a new generation of antiretrovirals for the treatment and prophylaxis. Antibodies are generally considered more effective and safer and have been proved to provide passive protection against mucosal challenge in humanized mice ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2016.00391

    authors: Sun M,Li Y,Zheng H,Shao Y

    更新日期:2016-09-30 00:00:00

  • A Rosetta Stone for Breast Cancer: Prognostic Value and Dynamic Regulation of Neutrophil in Tumor Microenvironment.

    abstract::Increasing evidence has revealed that the initiation and progression of breast cancer are greatly affected by the immune environment. Neutrophils are the most abundant leucocytes in circulation and act as the spearhead in inflammation, including in breast cancer. Circulating neutrophils are closely related to the prog...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2020.01779

    authors: Zhang W,Shen Y,Huang H,Pan S,Jiang J,Chen W,Zhang T,Zhang C,Ni C

    更新日期:2020-08-07 00:00:00

  • Reference Grade Characterization of Polymorphisms in Full-Length HLA Class I and II Genes With Short-Read Sequencing on the ION PGM System and Long-Reads Generated by Single Molecule, Real-Time Sequencing on the PacBio Platform.

    abstract::Although NGS technologies fuel advances in high-throughput HLA genotyping methods for identification and classification of HLA genes to assist with precision medicine efforts in disease and transplantation, the efficiency of these methods are impeded by the absence of adequately-characterized high-frequency HLA allele...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.02294

    authors: Suzuki S,Ranade S,Osaki K,Ito S,Shigenari A,Ohnuki Y,Oka A,Masuya A,Harting J,Baybayan P,Kitazume M,Sunaga J,Morishima S,Morishima Y,Inoko H,Kulski JK,Shiina T

    更新日期:2018-10-04 00:00:00

  • Curcumin Attenuates Titanium Particle-Induced Inflammation by Regulating Macrophage Polarization In Vitro and In Vivo.

    abstract::Periprosthetic inflammatory osteolysis and subsequent aseptic loosening are commonly observed in total joint arthroplasty. Other than revision surgery, few approved treatments are available for this complication. Wear particle-induced inflammation and macrophage polarization state play critical roles in periprosthetic...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.00055

    authors: Li B,Hu Y,Zhao Y,Cheng M,Qin H,Cheng T,Wang Q,Peng X,Zhang X

    更新日期:2017-01-31 00:00:00

  • Cytokine-Based Generation of CD49a+Eomes-/+ Natural Killer Cell Subsets.

    abstract::Recent studies have identified CD49a+Eomes- and CD49a+Eomes+ subsets of tissue-resident NK (trNK) cells in different organs of the mouse. However, the characteristics of CD49a+Eomes-/+ NK cell development and the regulation of Eomes expression in NK cells remain unclear. Here, we established an in vitro cytokine-based...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.02126

    authors: Ni X,Fu B,Zhang J,Sun R,Tian Z,Wei H

    更新日期:2018-09-25 00:00:00

  • Dysregulated TRAF3 and BCL2 Expression Promotes Multiple Classes of Mature Non-hodgkin B Cell Lymphoma in Mice.

    abstract::TNF-Receptor Associated Factor (TRAF)-3 is a master regulator of B cell homeostasis and function. TRAF3 has been shown to bind and regulate various proteins involved in the control of innate and adaptive immune responses. Previous studies showed that TRAF3 overexpression renders B cells hyper-reactive to antigens and ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.03114

    authors: Perez-Chacon G,Adrados M,Vallejo-Cremades MT,Lefebvre S,Reed JC,Zapata JM

    更新日期:2019-01-11 00:00:00

  • Squamous Cell Carcinomas of the Head and Neck Cancer Response to Programmed Cell Death Protein-1 Targeting and Differential Expression of Immunological Markers: A Case Report.

    abstract::Targeting the programmed cell death protein-1 (PD-1)/PD-1 ligand (PD-L1) pathway has been shown to enhance T cell-mediated antitumor immunity. Clinical responses are limited to subgroups of patients. The search for biomarkers of response is a strategy to predict response and outcome of PD-1/PD-L1 checkpoint interventi...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.01769

    authors: Merhi M,Raza A,Inchakalody VP,Nashwan AJJ,Allahverdi N,Krishnankutty R,Uddin S,Zar Gul AR,Al Homsi MU,Dermime S

    更新日期:2018-07-30 00:00:00

  • Debug Your Bugs - How NLRs Shape Intestinal Host-Microbe Interactions.

    abstract::The host's ability to discriminate friend and foe and to establish a precise homeostasis with its associated microbiota is crucial for its survival and fitness. Among the mediators of intestinal host-microbe interactions, NOD-like receptor (NLR) proteins take center stage. They are present in the epithelial lining and...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2013.00479

    authors: Lipinski S,Rosenstiel P

    更新日期:2013-12-27 00:00:00

  • Effects of the Positive Threshold and Data Analysis on Human MOG Antibody Detection by Live Flow Cytometry.

    abstract::Human autoantibodies targeting myelin oligodendrocyte glycoprotein (MOG Ab) have become a useful clinical biomarker for the diagnosis of a spectrum of inflammatory demyelinating disorders. Live cell-based assays that detect MOG Ab against conformational MOG are currently the gold standard. Flow cytometry, in which ser...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.00119

    authors: Tea F,Pilli D,Ramanathan S,Lopez JA,Merheb V,Lee FXZ,Zou A,Liyanage G,Bassett CB,Thomsen S,Reddel SW,Barnett MH,Brown DA,Dale RC,Brilot F,Australasian New Zealand MOG Study Group.

    更新日期:2020-02-06 00:00:00

  • Deletion of the Mineralocorticoid Receptor in Myeloid Cells Attenuates Central Nervous System Autoimmunity.

    abstract::Myeloid cells play an important role in the pathogenesis of multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). Monocytes, macrophages, and microglia can adopt two distinct phenotypes, with M1-polarized cells being more related to inflammation and autoimmunity while M2-polariz...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.01319

    authors: Montes-Cobos E,Schweingruber N,Li X,Fischer HJ,Reichardt HM,Lühder F

    更新日期:2017-10-13 00:00:00

  • Nanoparticle Interactions with the Immune System: Clinical Implications for Liposome-Based Cancer Chemotherapy.

    abstract::The development of stable and long-circulating liposomes provides protection of the drug cargo from degradation and increases tumor drug delivery, leading to the design of liposome formulations with great potential in cancer therapy. However, despite the sound pharmacologic basis, many liposomal as well as other nanop...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.00416

    authors: La-Beck NM,Gabizon AA

    更新日期:2017-04-06 00:00:00

  • Specific Strains of Lactic Acid Bacteria Differentially Modulate the Profile of Adipokines In Vitro.

    abstract::Obesity induces local/systemic inflammation accompanied by increases in macrophage infiltration into adipose tissue and production of inflammatory cytokines, chemokines, and hormones. Previous studies have shown that probiotics could improve the intestinal dysbiosis induced by metabolic diseases such as obesity, diabe...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.00266

    authors: Fabersani E,Abeijon-Mukdsi MC,Ross R,Medina R,González S,Gauffin-Cano P

    更新日期:2017-03-13 00:00:00

  • TLR3 Ligand PolyI:C Prevents Acute Pancreatitis Through the Interferon-β/Interferon-α/β Receptor Signaling Pathway in a Caerulein-Induced Pancreatitis Mouse Model.

    abstract::Acute pancreatitis (AP) is a common and devastating inflammatory disorder of the pancreas. However, there are still no effective treatments available for the disease. Therefore, it is important to discover new therapeutic targets and strategies for better treatment and prognosis of AP patients. Toll-like receptor 3 (T...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.00980

    authors: Huang C,Chen S,Zhang T,Li D,Huang Z,Huang J,Qin Y,Chen B,Cheng G,Ma F,Zhou M

    更新日期:2019-05-03 00:00:00

  • Intravital Microscopic Evaluation of the Effects of a CXCR2 Antagonist in a Model of Liver Ischemia Reperfusion Injury in Mice.

    abstract:Background:Ischemia-reperfusion (IR) is a major contributor to graft rejection after liver transplantation. During IR injury, an intense inflammatory process occurs in the liver. Neutrophils are considered central players in the events that lead to liver injury. CXC chemokines mediate hepatic inflammation following rep...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.01917

    authors: de Oliveira THC,Marques PE,Poosti F,Ruytinx P,Amaral FA,Brandolini L,Allegretti M,Proost P,Teixeira MM

    更新日期:2018-01-05 00:00:00

  • Cell of Origin and Genetic Alterations in the Pathogenesis of Multiple Myeloma.

    abstract::B cell activation and differentiation yields plasma cells with high affinity antibodies to a given antigen in a time-frame that allows for host protection. Although the end product is most commonly humoral immunity, the rapid proliferation and somatic mutation of the B cell receptor also results in oncogenic mutations...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2019.01121

    authors: Barwick BG,Gupta VA,Vertino PM,Boise LH

    更新日期:2019-05-21 00:00:00

  • Host-Microbe-Pathogen Interactions: A Review of Vibrio cholerae Pathogenesis in Drosophila.

    abstract::Most animals maintain mutually beneficial symbiotic relationships with their intestinal microbiota. Resident microbes in the gastrointestinal tract breakdown indigestible food, provide essential nutrients, and, act as a barrier against invading microbes, such as the enteric pathogen Vibrio cholerae. Over the last deca...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2019.03128

    authors: Davoodi S,Foley E

    更新日期:2020-01-24 00:00:00

  • Targeting Interleukin-2-Inducible T-Cell Kinase (ITK) Differentiates GVL and GVHD in Allo-HSCT.

    abstract::Allogeneic hematopoietic stem cell transplantation is a potentially curative procedure for many malignant diseases. Donor T cells prevent disease recurrence via graft-versus-leukemia (GVL) effect. Donor T cells also contribute to graft-versus-host disease (GVHD), a debilitating and potentially fatal complication. Nove...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.593863

    authors: Mammadli M,Huang W,Harris R,Sultana A,Cheng Y,Tong W,Pu J,Gentile T,Dsouza S,Yang Q,Bah A,August A,Karimi M

    更新日期:2020-11-26 00:00:00

  • Identifying the Presence of Prostate Cancer in Individuals with PSA Levels

    abstract::Determining whether an asymptomatic individual with Prostate-Specific Antigen (PSA) levels below 20 ng ml-1 has prostate cancer in the absence of definitive, biopsy-based evidence continues to present a significant challenge to clinicians who must decide whether such individuals with low PSA values have prostate cance...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.01771

    authors: Cosma G,McArdle SE,Reeder S,Foulds GA,Hood S,Khan M,Pockley AG

    更新日期:2017-12-18 00:00:00

  • Bacillus Calmette-Guérin-Induced Trained Immunity Is Not Protective for Experimental Influenza A/Anhui/1/2013 (H7N9) Infection in Mice.

    abstract::Avian influenza A of the subtype H7N9 has been responsible for almost 1,600 confirmed human infections and more than 600 deaths since its first outbreak in 2013. Although sustained human-to-human transmission has not been reported yet, further adaptations to humans in the viral genome could potentially lead to an infl...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.00869

    authors: de Bree LCJ,Marijnissen RJ,Kel JM,Rosendahl Huber SK,Aaby P,Benn CS,Wijnands MVW,Diavatopoulos DA,van Crevel R,Joosten LAB,Netea MG,Dulos J

    更新日期:2018-04-30 00:00:00

  • Targeting 4-1BB (CD137) to enhance CD8 T cell responses with poxviruses and viral antigens.

    abstract::Attenuated vaccinia virus (VACV) vectors are considered prime vaccine candidates for use in immunotherapy of infectious disease. In spite of this, recent data show that the level of attenuation may hamper the efficient generation of protective CD8 T cells. This suggests that additional adjuvant-like activities may nee...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2012.00332

    authors: Zhao Y,Tahiliani V,Salek-Ardakani S,Croft M

    更新日期:2012-11-08 00:00:00

  • Endothelial Basement Membrane Laminins as an Environmental Cue in Monocyte Differentiation to Macrophages.

    abstract::Monocyte differentiation to macrophages is triggered by migration across the endothelial barrier, which is constituted by both endothelial cells and their underlying basement membrane. We address here the role of the endothelial basement membrane laminins (laminins 411 and 511) in this monocyte to macrophage switch. C...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.584229

    authors: Li L,Song J,Chuquisana O,Hannocks MJ,Loismann S,Vogl T,Roth J,Hallmann R,Sorokin L

    更新日期:2020-10-30 00:00:00

  • Human Serum Albumin Binds Streptolysin O (SLO) Toxin Produced by Group A Streptococcus and Inhibits Its Cytotoxic and Hemolytic Effects.

    abstract::The pathogenicity of group A Streptococcus (GAS) is mediated by direct bacterial invasivity and toxin-associated damage. Among the extracellular products, the exotoxin streptolysin O (SLO) is produced by almost all GAS strains. SLO is a pore forming toxin (PFT) hemolitically active and extremely toxic in vivo. Recent ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.507092

    authors: Vita GM,De Simone G,Leboffe L,Montagnani F,Mariotti D,Di Bella S,Luzzati R,Gori A,Ascenzi P,di Masi A

    更新日期:2020-12-08 00:00:00

  • Eosinophil Extracellular Traps and Inflammatory Pathologies-Untangling the Web!

    abstract::Eosinophils are an enigmatic white blood cell, whose immune functions are still under intense investigation. Classically, the eosinophil was considered to fulfill a protective role against parasitic infections, primarily large multicellular helminths. Although eosinophils are predominantly associated with parasite inf...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2018.02763

    authors: Mukherjee M,Lacy P,Ueki S

    更新日期:2018-11-26 00:00:00

  • Dissecting the Immune Stimulation Promoted by CSF-470 Vaccine Plus Adjuvants in Cutaneous Melanoma Patients: Long Term Antitumor Immunity and Short Term Release of Acute Inflammatory Reactants.

    abstract::As cutaneous melanoma (CM) currently remains with a bleak prognosis, thorough investigation of new treatment options are of utmost relevance. In the phase II/III randomized clinical trial (CASVAC-0401), the repeated immunization of stages IIB-III CM patients with the irradiated, allogeneic cellular CSF-470 vaccine plu...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.02531

    authors: Pampena MB,Cartar HC,Cueto GR,Levy EM,Blanco PA,Barrio MM,Mordoh J

    更新日期:2018-11-02 00:00:00

  • Dynamics of Natural Killer Cells Cytotoxicity in Microwell Arrays with Connecting Channels.

    abstract::Natural killer (NK) cells serve an important role in immune system by recognizing and killing the potentially malignant cells without antigen sensitization, and could be promising in cancer therapy. We have designed and fabricated microwell arrays with microchannel connections in polydimethylsiloxane (PDMS) substrates...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.00998

    authors: Xu Y,Zhou S,Lam YW,Pang SW

    更新日期:2017-08-17 00:00:00

  • Immunological Aspects of Approved MS Therapeutics.

    abstract::Multiple sclerosis (MS) is the most common neurological immune-mediated disease leading to disability in young adults. The outcome of the disease is unpredictable, and over time, neurological disabilities accumulate. Interferon beta-1b was the first drug to be approved in the 1990s for relapsing-remitting MS to modula...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2019.01564

    authors: Rommer PS,Milo R,Han MH,Satyanarayan S,Sellner J,Hauer L,Illes Z,Warnke C,Laurent S,Weber MS,Zhang Y,Stuve O

    更新日期:2019-07-11 00:00:00