Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
9.0
6.0
Journals
Cells
Special Issues
Immunology of Cell Death in Cancer Immunotherapy
share announcement

Immunology of Cell Death in Cancer Immunotherapy

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Immunology".

Deadline for manuscript submissions: closed (15 December 2020) | Viewed by 59869

Special Issue Editors

Prof. Abhishek D. Garg

grade E-Mail Website
Guest Editor
Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium
Interests: immunology of cell death; cancer immunology; immunotherapy; innate immune system–cancer cell death crosstalk
Dr. Lorenzo Galluzzi

grade E-Mail Website
Guest Editor
Weill Cornell Medical College, Stich Radiation Oncology, 525 East 68th Street, Box # 169, New York, NY 10065, USA
Interests: immunology of cell death; cancer immunology; links between cellular adaptation to stress and maintenance of organismal homeostasis

Special Issue Information

Dear Colleagues,

Dead or dying cancer cells can have robust immunomodulatory effects that strongly influence the success of cancer immunotherapy. Therapy-induced cancer cell death generally occurs by regulated cell death programs that, depending on the context, can either aid or impede the initiation of anticancer immunity. Cancer cell death can be accompanied by the secretion or release of specific cytokines, chemokines, metabolites, danger signals (or alarmins) and post-translationally or proteolytically modified biomolecules that, together with the nature of cell death pathway, define the immunological impact of cancer cell death. Notably, a specific combination of danger signals, cytokines, chemokines and metabolites can support immunological reactions that drive cancer antigen-specific T cell immunity, thereby enforcing durable tumour regression. This is especially applicable to immunogenic cell death (ICD), an apoptotic or necroptotic cell death modality that is induced by a range of conventional anticancer agents encompassing conventional chemotherapeutics, radiation therapy and targeted anticancer agents.

In recent times, considerable effort has been devoted to understanding how the innate and adaptive immune system perceive and decode various major cell death pathways in dynamic settings characterized by multi-factorial signalling. However, an integrated view of cancer cell death immunology that can be reliably exploited for highly efficacious cancer immunotherapy remains enigmatic. The aim of this Special Issue is to bring together researchers working on immunology of cell death in cancer and foster a comprehensive discussion on how immunological characteristics of dying or dead cancer cells can be exploited for improving cancer immunotherapy. We anticipate that this special edition will provide a comprehensive description of the main molecular, immunological, preclinical, and clinical aspects of cancer cell death immunology.

Prof. Abhishek D. Garg
Prof. Lorenzo Galluzzi
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • apoptosis
  • cancer immunology
  • cancer immunotherapy
  • ferroptosis
  • immunity
  • immunogenic cell death
  • immuno-oncology
  • inflammation
  • necroptosis
  • necrosis
  • programmed cell death

Published Papers (11 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Editorial

Jump to: Research, Review

7 pages, 212 KiB  
Editorial
Immunology of Cell Death in Cancer Immunotherapy
by Lorenzo Galluzzi and Abhishek D. Garg
Cells 2021, 10(5), 1208; https://doi.org/10.3390/cells10051208 - 15 May 2021
Cited by 9 | Viewed by 3112
Abstract
Over the last two decades, a large volume of studies has established that dying and dead cancer cells exert a potent immunomodulatory effect on their immediate microenvironment, which has a major influence on the anticancer immunity [...] Full article
(This article belongs to the Special Issue Immunology of Cell Death in Cancer Immunotherapy)

Research

Jump to: Editorial, Review

16 pages, 5945 KiB  
Article
Identification of 15 lncRNAs Signature for Predicting Survival Benefit of Advanced Melanoma Patients Treated with Anti-PD-1 Monotherapy
by Jian-Guo Zhou, Bo Liang, Jian-Guo Liu, Su-Han Jin, Si-Si He, Benjamin Frey, Ning Gu, Rainer Fietkau, Markus Hecht, Hu Ma and Udo S. Gaipl
Cells 2021, 10(5), 977; https://doi.org/10.3390/cells10050977 - 22 Apr 2021
Cited by 24 | Viewed by 2870
Abstract
The blockade of programmed cell death protein 1 (PD-1) as monotherapy has been widely used in melanoma, but to identify melanoma patients with survival benefit from anti-PD-1 monotherapy is still a big challenge. There is an urgent need for prognostic signatures improving the [...] Read more.
The blockade of programmed cell death protein 1 (PD-1) as monotherapy has been widely used in melanoma, but to identify melanoma patients with survival benefit from anti-PD-1 monotherapy is still a big challenge. There is an urgent need for prognostic signatures improving the prediction of immunotherapy responses of these patients. We analyzed transcriptomic data of pre-treatment tumor biopsies and clinical profiles in advanced melanoma patients receiving only anti-PD-1 monotherapy (nivolumab or pembrolizumab) from the PRJNA356761 and PRJEB23709 data sets as the training and validation cohort, respectively. Weighted gene co-expression network analysis was used to identify the key module, then least absolute shrinkage and selection operator was conducted to determine prognostic-related long noncoding RNAs (lncRNAs). Subsequently, the differentially expressed genes between different clusters were identified, and their function and pathway annotation were performed. In this investigation, 92 melanoma patients with complete survival information (51 from training cohort and 41 from validation cohort) were included in our analyses. We initiallyidentified the key module (skyblue) by weighted gene co-expression network analysis, and then identified a 15 predictive lncRNAs (AC010904.2, LINC01126, AC012360.1, AC024933.1, AL442128.2, AC022211.4, AC022211.2, AC127496.5, NARF-AS1, AP000919.3, AP005329.2, AC023983.1, AC023983.2, AC139100.1, and AC012615.4) signature in melanoma patients treated with anti-PD-1 monotherapy by least absolute shrinkage and selection operator in the training cohort. These results were then validated in the validation cohort. Finally, enrichment analysis showed that the functions of differentially expressed genes between two consensus clusters were mainly related to the immune process and treatment. In summary, the 15 lncRNAs signature is a novel effective predictor for prognosis in advanced melanoma patients treated with anti-PD-1 monotherapy. Full article
(This article belongs to the Special Issue Immunology of Cell Death in Cancer Immunotherapy)
►▼ Show Figures

Graphical abstract

17 pages, 2704 KiB  
Article
Clinically Relevant Chemotherapeutics Have the Ability to Induce Immunogenic Cell Death in Non-Small Cell Lung Cancer
by Tal Flieswasser, Jinthe Van Loenhout, Laurie Freire Boullosa, Astrid Van den Eynde, Jorrit De Waele, Jonas Van Audenaerde, Filip Lardon, Evelien Smits, Patrick Pauwels and Julie Jacobs
Cells 2020, 9(6), 1474; https://doi.org/10.3390/cells9061474 - 16 Jun 2020
Cited by 38 | Viewed by 4255
Abstract
The concept of immunogenic cell death (ICD) has emerged as a cornerstone of therapy-induced anti-tumor immunity. To this end, the following chemotherapies were evaluated for their ability to induce ICD in non-small cell lung cancer (NSCLC) cell lines: docetaxel, carboplatin, cisplatin, oxaliplatin and [...] Read more.
The concept of immunogenic cell death (ICD) has emerged as a cornerstone of therapy-induced anti-tumor immunity. To this end, the following chemotherapies were evaluated for their ability to induce ICD in non-small cell lung cancer (NSCLC) cell lines: docetaxel, carboplatin, cisplatin, oxaliplatin and mafosfamide. The ICD hallmarks ATP, ecto-calreticulin, HMGB1, phagocytosis and maturation status of dendritic cells (DCs) were assessed in vitro. Furthermore, an in vivo vaccination assay on C57BL/6J mice was performed to validate our in vitro results. Docetaxel and the combination of docetaxel with carboplatin or cisplatin demonstrated the highest levels of ATP, ecto-calreticulin and HMGB1 in three out of four NSCLC cell lines. In addition, these regimens resulted in phagocytosis of treated NSCLC cells and maturation of DCs. Along similar lines, all mice vaccinated with NSCLC cells treated with docetaxel and cisplatin remained tumor-free after challenge. However, this was not the case for docetaxel, despite its induction of the ICD-related molecules in vitro, as it failed to reject tumor growth at the challenge site in 60% of the mice. Moreover, our in vitro and in vivo data show the inability of oxaliplatin to induce ICD in NSCLC cells. Overall with this study we demonstrate that clinically relevant chemotherapeutic regimens in NSCLC patients have the ability to induce ICD. Full article
(This article belongs to the Special Issue Immunology of Cell Death in Cancer Immunotherapy)
►▼ Show Figures

Figure 1

17 pages, 3722 KiB  
Article
Insights into P-Glycoprotein Inhibitors: New Inducers of Immunogenic Cell Death
by Joanna Kopecka, Martina Godel, Silvia Dei, Roberta Giampietro, Dimas Carolina Belisario, Muhlis Akman, Marialessandra Contino, Elisabetta Teodori and Chiara Riganti
Cells 2020, 9(4), 1033; https://doi.org/10.3390/cells9041033 - 22 Apr 2020
Cited by 22 | Viewed by 4116
Abstract
Doxorubicin is a strong inducer of immunogenic cell death (ICD), but it is ineffective in P-glycoprotein (Pgp)-expressing cells. Indeed, Pgp effluxes doxorubicin and impairs the immunesensitizing functions of calreticulin (CRT), an “eat-me” signal mediating ICD. It is unknown if classical Pgp inhibitors, designed [...] Read more.
Doxorubicin is a strong inducer of immunogenic cell death (ICD), but it is ineffective in P-glycoprotein (Pgp)-expressing cells. Indeed, Pgp effluxes doxorubicin and impairs the immunesensitizing functions of calreticulin (CRT), an “eat-me” signal mediating ICD. It is unknown if classical Pgp inhibitors, designed to reverse chemoresistance, may restore ICD. We addressed this question by using Pgp-expressing cancer cells, treated with Tariquidar, a clinically approved Pgp inhibitor, and R-3 compound, a N,N-bis(alkanol)amine aryl ester derivative with the same potency of Tariquidar as Pgp inhibitor. In Pgp-expressing/doxorubicin-resistant cells, Tariquidar and R-3 increased doxorubicin accumulation and toxicity, reduced Pgp activity, and increased CRT translocation and ATP and HMGB1 release. Unexpectedly, only R-3 promoted phagocytosis by dendritic cells and activation of antitumor CD8+T-lymphocytes. Although Tariquidar did not alter the amount of Pgp present on cell surface, R-3 promoted Pgp internalization and ubiquitination, disrupting its interaction with CRT. Pgp knock-out restores doxorubicin-induced ICD in MDA-MB-231/DX cells that recapitulated the phenotype of R-3-treated cells. Our work demonstrates that plasma membrane-associated Pgp prevents a complete ICD notwithstanding the release of ATP and HMGB1, and the exposure of CRT. Pharmacological compounds reducing Pgp activity and amount may act as promising chemo- and immunesensitizing agents. Full article
(This article belongs to the Special Issue Immunology of Cell Death in Cancer Immunotherapy)
►▼ Show Figures

Figure 1

21 pages, 5292 KiB  
Article
Tumor-Intrinsic or Drug-Induced Immunogenicity Dictates the Therapeutic Success of the PD1/PDL Axis Blockade
by Alessandra Rossi, Valeria Lucarini, Iole Macchia, Paola Sestili, Carla Buccione, Simona Donati, Maria Ciccolella, Antonella Sistigu, Maria Teresa D’Urso, Anna Maria Pacca, Enrico Cardarelli, Fabrizio Mattei, Enrico Proietti, Giovanna Schiavoni and Laura Bracci
Cells 2020, 9(4), 940; https://doi.org/10.3390/cells9040940 - 10 Apr 2020
Cited by 8 | Viewed by 3568
Abstract
Immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment providing unprecedented clinical benefits. However, many patients do not respond to ICIs as monotherapy or develop resistance. Combining ICI-based immunotherapy with chemotherapy is a promising strategy to increase response rates, but few rationale-driven [...] Read more.
Immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment providing unprecedented clinical benefits. However, many patients do not respond to ICIs as monotherapy or develop resistance. Combining ICI-based immunotherapy with chemotherapy is a promising strategy to increase response rates, but few rationale-driven chemo-immunotherapy combinations have reached the clinical arena thus far. In the present study, we show that combined anti-PDL1 and anti-PDL2 antibodies optimally synergize with cyclophosphamide but not with cisplatin, and that the magnitude and duration of the therapeutic response is dependent on the immunogenic potential of the drug and of the tumor itself. Hallmarks of successful therapeutic outcomes were the enhanced infiltration by myeloid (mainly cross-presenting dendritic cells, eosinophils, and monocytic myeloid cells) and T lymphocytes into the tumor tissue and the expansion of circulating memory pools. Overall, our results suggest that immunomodulating chemotherapy can be exploited to increase the efficacy of PD1/PDL axis inhibitors in vivo, and that the magnitude of the synergic therapeutic response is affected by tumor-intrinsic immunogenicity. Full article
(This article belongs to the Special Issue Immunology of Cell Death in Cancer Immunotherapy)
►▼ Show Figures

Figure 1

13 pages, 1730 KiB  
Article
TNFa and IL2 Encoding Oncolytic Adenovirus Activates Pathogen and Danger-Associated Immunological Signaling
by Camilla Heiniö, Riikka Havunen, Joao Santos, Klaas de Lint, Victor Cervera-Carrascon, Anna Kanerva and Akseli Hemminki
Cells 2020, 9(4), 798; https://doi.org/10.3390/cells9040798 - 26 Mar 2020
Cited by 27 | Viewed by 3119
Abstract
In order to break tumor resistance towards traditional treatments, we investigate the response of tumor and immune cells to a novel, cytokine-armed oncolytic adenovirus: Ad5/3-d24-E2F-hTNFa-IRES-hIL2 (also known as TILT-123 and OAd.TNFa-IL2). There are several pattern recognition receptors (PRR) that might mediate adenovirus-infection recognition. [...] Read more.
In order to break tumor resistance towards traditional treatments, we investigate the response of tumor and immune cells to a novel, cytokine-armed oncolytic adenovirus: Ad5/3-d24-E2F-hTNFa-IRES-hIL2 (also known as TILT-123 and OAd.TNFa-IL2). There are several pattern recognition receptors (PRR) that might mediate adenovirus-infection recognition. However, the role and specific effects of each PRR on the tumor microenvironment and treatment outcome remain unclear. Hence, the aim of this study was to investigate the effects of OAd.TNFa-IL2 infection on PRR-mediated danger- and pathogen-associated molecular pattern (DAMP and PAMP, respectively) signaling. In addition, we wanted to see which PRRs mediate an antitumor response and are therefore relevant for optimizing this virotherapy. We determined that OAd.TNFa-IL2 induced DAMP and PAMP release and consequent tumor microenvironment modulation. We show that the AIM2 inflammasome is activated during OAd.TNFa-IL2 virotherapy, thus creating an immunostimulatory antitumor microenvironment. Full article
(This article belongs to the Special Issue Immunology of Cell Death in Cancer Immunotherapy)
►▼ Show Figures

Figure 1

Review

Jump to: Editorial, Research

16 pages, 311 KiB  
Review
Biomarkers of Radiotherapy-Induced Immunogenic Cell Death
by Rianne D. W. Vaes, Lizza E. L. Hendriks, Marc Vooijs and Dirk De Ruysscher
Cells 2021, 10(4), 930; https://doi.org/10.3390/cells10040930 - 17 Apr 2021
Cited by 55 | Viewed by 4551
Abstract
Radiation therapy (RT) can induce an immunogenic variant of regulated cell death that can initiate clinically relevant tumor-targeting immune responses. Immunogenic cell death (ICD) is accompanied by the exposure and release of damage-associated molecular patterns (DAMPs), chemokine release, and stimulation of type I [...] Read more.
Radiation therapy (RT) can induce an immunogenic variant of regulated cell death that can initiate clinically relevant tumor-targeting immune responses. Immunogenic cell death (ICD) is accompanied by the exposure and release of damage-associated molecular patterns (DAMPs), chemokine release, and stimulation of type I interferon (IFN-I) responses. In recent years, intensive research has unraveled major mechanistic aspects of RT-induced ICD and has resulted in the identification of immunogenic factors that are released by irradiated tumor cells. However, so far, only a limited number of studies have searched for potential biomarkers that can be used to predict if irradiated tumor cells undergo ICD that can elicit an effective immunogenic anti-tumor response. In this article, we summarize the available literature on potential biomarkers of RT-induced ICD that have been evaluated in cancer patients. Additionally, we discuss the clinical relevance of these findings and important aspects that should be considered in future studies. Full article
(This article belongs to the Special Issue Immunology of Cell Death in Cancer Immunotherapy)
24 pages, 3458 KiB  
Review
Cell Death in the Tumor Microenvironment: Implications for Cancer Immunotherapy
by Varsha Gadiyar, Kevin C. Lahey, David Calianese, Connor Devoe, Dhriti Mehta, Kristy Bono, Samuel Desind, Viralkumar Davra and Raymond B. Birge
Cells 2020, 9(10), 2207; https://doi.org/10.3390/cells9102207 - 29 Sep 2020
Cited by 18 | Viewed by 6153
Abstract
The physiological fate of cells that die by apoptosis is their prompt and efficient removal by efferocytosis. During these processes, apoptotic cells release intracellular constituents that include purine nucleotides, lysophosphatidylcholine (LPC), and Sphingosine-1-phosphate (S1P) that induce migration and chemo-attraction of phagocytes as well [...] Read more.
The physiological fate of cells that die by apoptosis is their prompt and efficient removal by efferocytosis. During these processes, apoptotic cells release intracellular constituents that include purine nucleotides, lysophosphatidylcholine (LPC), and Sphingosine-1-phosphate (S1P) that induce migration and chemo-attraction of phagocytes as well as mitogens and extracellular membrane-bound vesicles that contribute to apoptosis-induced compensatory proliferation and alteration of the extracellular matrix and the vascular network. Additionally, during efferocytosis, phagocytic cells produce a number of anti-inflammatory and resolving factors, and, together with apoptotic cells, efferocytic events have a homeostatic function that regulates tissue repair. These homeostatic functions are dysregulated in cancers, where, aforementioned events, if not properly controlled, can lead to cancer progression and immune escape. Here, we summarize evidence that apoptosis and efferocytosis are exploited in cancer, as well as discuss current translation and clinical efforts to harness signals from dying cells into therapeutic strategies. Full article
(This article belongs to the Special Issue Immunology of Cell Death in Cancer Immunotherapy)
►▼ Show Figures

Figure 1

30 pages, 2229 KiB  
Review
Necroptosis in Immuno-Oncology and Cancer Immunotherapy
by Jenny Sprooten, Pieter De Wijngaert, Isaure Vanmeerbeek, Shaun Martin, Peter Vangheluwe, Susan Schlenner, Dmitri V. Krysko, Jan B. Parys, Geert Bultynck, Peter Vandenabeele and Abhishek D. Garg
Cells 2020, 9(8), 1823; https://doi.org/10.3390/cells9081823 - 01 Aug 2020
Cited by 102 | Viewed by 9435
Abstract
Immune-checkpoint blockers (ICBs) have revolutionized oncology and firmly established the subfield of immuno-oncology. Despite this renaissance, a subset of cancer patients remain unresponsive to ICBs due to widespread immuno-resistance. To “break” cancer cell-driven immuno-resistance, researchers have long floated the idea of therapeutically facilitating [...] Read more.
Immune-checkpoint blockers (ICBs) have revolutionized oncology and firmly established the subfield of immuno-oncology. Despite this renaissance, a subset of cancer patients remain unresponsive to ICBs due to widespread immuno-resistance. To “break” cancer cell-driven immuno-resistance, researchers have long floated the idea of therapeutically facilitating the immunogenicity of cancer cells by disrupting tumor-associated immuno-tolerance via conventional anticancer therapies. It is well appreciated that anticancer therapies causing immunogenic or inflammatory cell death are best positioned to productively activate anticancer immunity. A large proportion of studies have emphasized the importance of immunogenic apoptosis (i.e., immunogenic cell death or ICD); yet, it has also emerged that necroptosis, a programmed necrotic cell death pathway, can also be immunogenic. Emergence of a proficient immune profile for necroptosis has important implications for cancer because resistance to apoptosis is one of the major hallmarks of tumors. Putative immunogenic or inflammatory characteristics driven by necroptosis can be of great impact in immuno-oncology. However, as is typical for a highly complex and multi-factorial disease like cancer, a clear cause versus consensus relationship on the immunobiology of necroptosis in cancer cells has been tough to establish. In this review, we discuss the various aspects of necroptosis immunobiology with specific focus on immuno-oncology and cancer immunotherapy. Full article
(This article belongs to the Special Issue Immunology of Cell Death in Cancer Immunotherapy)
►▼ Show Figures

Graphical abstract

24 pages, 1394 KiB  
Review
Modulation of Determinant Factors to Improve Therapeutic Combinations with Immune Checkpoint Inhibitors
by Magalie Dosset, Elodie Lauret-Marie Joseph, Thaiz Rivera Vargas and Lionel Apetoh
Cells 2020, 9(7), 1727; https://doi.org/10.3390/cells9071727 - 19 Jul 2020
Cited by 7 | Viewed by 3804
Abstract
Immune checkpoint inhibitors (ICPi) have shown their superiority over conventional therapies to treat some cancers. ICPi are effective against immunogenic tumors. However, patients with tumors poorly infiltrated with immune cells do not respond to ICPi. Combining ICPi with other anticancer therapies such as [...] Read more.
Immune checkpoint inhibitors (ICPi) have shown their superiority over conventional therapies to treat some cancers. ICPi are effective against immunogenic tumors. However, patients with tumors poorly infiltrated with immune cells do not respond to ICPi. Combining ICPi with other anticancer therapies such as chemotherapy, radiation, or vaccines, which can stimulate the immune system and recruit antitumor T cells into the tumor bed, may be a relevant strategy to increase the proportion of responding patients. Such an approach still raises the following questions: What are the immunological features modulated by immunogenic therapies that can be critical to ensure not only immediate but also long-lasting tumor protection? How must the combined treatments be administered to the patients to harness their full potential while limiting adverse immunological events? Here, we address these points by reviewing how immunogenic anticancer therapies can provide novel therapeutic opportunities upon combination with ICPi. We discuss their ability to create a permissive tumor microenvironment through the generation of inflamed tumors and stimulation of memory T cells such as resident (TRM) and stem-cell like (TSCM) cells. We eventually underscore the importance of sequence, dose, and duration of the combined anticancer therapies to design optimal and successful cancer immunotherapy strategies. Full article
(This article belongs to the Special Issue Immunology of Cell Death in Cancer Immunotherapy)
►▼ Show Figures

Figure 1

20 pages, 1796 KiB  
Review
Hypoxia-Driven Immune Escape in the Tumor Microenvironment
by Alyssa Vito, Nader El-Sayes and Karen Mossman
Cells 2020, 9(4), 992; https://doi.org/10.3390/cells9040992 - 16 Apr 2020
Cited by 138 | Viewed by 13439
Abstract
The tumor microenvironment is a complex ecosystem comprised of many different cell types, abnormal vasculature and immunosuppressive cytokines. The irregular growth kinetics with which tumors grow leads to increased oxygen consumption and, in turn, hypoxic conditions. Hypoxia has been associated with poor clinical [...] Read more.
The tumor microenvironment is a complex ecosystem comprised of many different cell types, abnormal vasculature and immunosuppressive cytokines. The irregular growth kinetics with which tumors grow leads to increased oxygen consumption and, in turn, hypoxic conditions. Hypoxia has been associated with poor clinical outcome, increased tumor heterogeneity, emergence of resistant clones and evasion of immune detection. Additionally, hypoxia-driven cell death pathways have traditionally been thought of as tolerogenic processes. However, as researchers working in the field of immunotherapy continue to investigate and unveil new types of immunogenic cell death (ICD), it has become clear that, in some instances, hypoxia may actually induce ICD within a tumor. In this review, we will discuss hypoxia-driven immune escape that drives poor prognostic outcomes, the ability of hypoxia to induce ICD and potential therapeutic targets amongst hypoxia pathways. Full article
(This article belongs to the Special Issue Immunology of Cell Death in Cancer Immunotherapy)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-11
Back to TopTop