Online citations, reference lists, and bibliographies.
Please confirm you are human
(Sign Up for free to never see this)
← Back to Search

Exploiting The Immunomodulatory Properties Of Chemotherapeutic Drugs To Improve The Success Of Cancer Immunotherapy

K. Kersten, Camilla Salvagno, K. D. de Visser
Published 2015 · Medicine

Save to my Library
Download PDF
Analyze on Scholarcy
Share
Cancer immunotherapy is gaining momentum in the clinic. The current challenge is to understand why a proportion of cancer patients do not respond to cancer immunotherapy, and how this can be translated into the rational design of combinatorial cancer immunotherapy strategies aimed at maximizing success of immunotherapy. Here, we discuss how tumors orchestrate an immunosuppressive microenvironment, which contributes to their escape from immune attack. Relieving the immunosuppressive networks in cancer patients is an attractive strategy to extend the clinical success of cancer immunotherapy. Since the clinical availability of drugs specifically targeting immunosuppressive cells or mediators is still limited, an alternative strategy is to use conventional chemotherapy drugs with immunomodulatory properties to improve cancer immunotherapy. We summarize the preclinical and clinical studies that illustrate how the anti-tumor T cell response can be enhanced by chemotherapy-induced relief of immunosuppressive networks. Treatment strategies aimed at combining chemotherapy-induced relief of immunosuppression and T cell-boosting checkpoint inhibitors provide an attractive and clinically feasible approach to overcome intrinsic and acquired resistance to cancer immunotherapy, and to extend the clinical success of cancer immunotherapy.
This paper references
10.1038/nm.2999
Chemotherapy-triggered cathepsin B release in myeloid-derived suppressor cells activates the Nlrp3 inflammasome and promotes tumor growth
M. Bruchard (2013)
10.1038/nature13111
Ultraviolet-radiation-induced inflammation promotes angiotropism and metastasis in melanoma
Tobias Bald (2014)
10.1038/nature10138
CCL2 recruits inflammatory monocytes to facilitate breast tumor metastasis
Bin-Zhi Qian (2011)
10.1038/nm1517
Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma
A. Parsa (2007)
10.1016/j.ccr.2009.06.018
CD4(+) T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages.
D. DeNardo (2009)
10.1038/nm1093
Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival
T. Curiel (2004)
10.1007/s00109-015-1286-y
Transcriptional programming of human macrophages: on the way to systems immunology
J. Schultze (2015)
10.4049/jimmunol.171.3.1232
l-Arginine Consumption by Macrophages Modulates the Expression of CD3ζ Chain in T Lymphocytes1
P. Rodriguez (2003)
10.1158/0008-5472.CAN-08-1921
Arginase I-producing myeloid-derived suppressor cells in renal cell carcinoma are a subpopulation of activated granulocytes.
P. Rodriguez (2009)
10.4049/jimmunol.167.10.5583
Tumor-Infiltrating Macrophages Induce Apoptosis in Activated CD8+ T Cells by a Mechanism Requiring Cell Contact and Mediated by Both the Cell-Associated Form of TNF and Nitric Oxide1
M. Saio (2001)
10.1053/j.seminoncol.2015.05.007
Immune Effects of Chemotherapy, Radiation, and Targeted Therapy and Opportunities for Combination With Immunotherapy.
J. Wargo (2015)
10.1093/INTIMM/DXM057
PD-1 and PD-1 ligands: from discovery to clinical application.
T. Okazaki (2007)
10.1084/jem.20130066
Indoleamine 2,3-dioxygenase is a critical resistance mechanism in antitumor T cell immunotherapy targeting CTLA-4
Rikke B. Holmgaard (2013)
10.1016/j.coi.2013.02.005
Genetically engineered mouse models of cancer reveal new insights about the antitumor immune response.
Michel DuPage (2013)
Tolllike receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy
L Apetoh (2007)
10.1038/nm.2652
Chemotherapy response of spontaneous mammary tumors is independent of the adaptive immune system
M. Ciampricotti (2012)
10.1126/science.aaa8172
The future of immune checkpoint therapy
P. Sharma (2015)
10.1016/j.ccell.2014.11.010
Dissecting the Tumor Myeloid Compartment Reveals Rare Activating Antigen-Presenting Cells Critical for T Cell Immunity.
M. Broz (2014)
10.1016/1074-7613(94)90071-X
CTLA-4 can function as a negative regulator of T cell activation.
T. Walunas (1994)
Breaking immune tolerance by targeting CD 25 + regulatory T cells is essential for the anti - tumor effect of the CTLA - 4 blockade in an HLA - DR transgenic mouse model of
EN Klyushnenkova
10.1002/ijc.25756
Gemcitabine depletes regulatory T‐cells in human and mice and enhances triggering of vaccine‐specific cytotoxic T‐cells
Lorna Rettig (2011)
10.1056/NEJMoa1200690
Safety, activity, and immune correlates of anti-PD-1 antibody in cancer.
S. Topalian (2012)
10.1038/nm.3773
High-throughput epitope discovery reveals frequent recognition of neo-antigens by CD4+ T cells in human melanoma
C. Linnemann (2015)
10.1007/s00262-012-1294-5
Neutrophils and granulocytic myeloid-derived suppressor cells: immunophenotyping, cell biology and clinical relevance in human oncology
C. Dumitru (2012)
10.1016/j.ccr.2014.05.016
Targeting tumor-associated macrophages with anti-CSF-1R antibody reveals a strategy for cancer therapy.
C. Ries (2014)
10.1016/J.CCR.2006.09.013
Somatic inactivation of E-cadherin and p53 in mice leads to metastatic lobular mammary carcinoma through induction of anoikis resistance and angiogenesis.
P. Derksen (2006)
10.1200/JCO.2014.59.0703
Nivolumab for Metastatic Renal Cell Carcinoma: Results of a Randomized Phase II Trial.
R. Motzer (2015)
10.1084/jem.20030152
Conversion of Peripheral CD4+CD25− Naive T Cells to CD4+CD25+ Regulatory T Cells by TGF-β Induction of Transcription Factor Foxp3
W. Chen (2003)
10.1056/NEJMoa1411087
PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma.
S. Ansell (2015)
10.1073/pnas.1015855107
Granulocyte-colony stimulating factor promotes lung metastasis through mobilization of Ly6G+Ly6C+ granulocytes
M. Kowanetz (2010)
Natural suppressor (NS) cells found in the spleen of neonatal mice and adult mice given total lymphoid irradiation (TLI) express the null surface phenotype.
A. Oseroff (1984)
10.1126/science.aaa6204
T cell exclusion, immune privilege, and the tumor microenvironment
J. Joyce (2015)
10.1158/0008-5472.CAN-11-2786
Genetically engineered mouse models: closing the gap between preclinical data and trial outcomes.
M. Singh (2012)
10.1084/JEM.193.6.727
Colony-Stimulating Factor 1 Promotes Progression of Mammary Tumors to Malignancy
E. Lin (2001)
10.1016/j.ccell.2014.09.006
Macrophage IL-10 blocks CD8+ T cell-dependent responses to chemotherapy by suppressing IL-12 expression in intratumoral dendritic cells.
B. Ruffell (2014)
10.1002/eji.200324181
CD4+CD25+ regulatory T cells suppress tumor immunity but are sensitive to cyclophosphamide which allows immunotherapy of established tumors to be curative
F. Ghiringhelli (2004)
IL-17-producing γδ T cells and neutrophils conspire to promote breast cancer metastasis
SB Coffelt (2015)
10.1200/jco.2015.33.18_suppl.lba100
PD-1 blockade in tumors with mismatch repair deficiency.
J. Uram (2015)
10.1158/2326-6066.CIR-14-0133
PD-L1 Expression Correlates with Tumor-Infiltrating Lymphocytes and Response to Neoadjuvant Chemotherapy in Breast Cancer
Hallie Wimberly (2014)
10.4049/jimmunol.1202088
Increased Myeloid-Derived Suppressor Cells in Gastric Cancer Correlate with Cancer Stage and Plasma S100A8/A9 Proinflammatory Proteins
L. Wang (2013)
10.1172/JCI40269
Chemotherapy enhances tumor cell susceptibility to CTL-mediated killing during cancer immunotherapy in mice.
R. Ramakrishnan (2010)
10.1182/BLOOD-2007-04-086835
Reversion of immune tolerance in advanced malignancy: modulation of myeloid-derived suppressor cell development by blockade of stem-cell factor function.
P. Pan (2008)
10.1126/scitranslmed.3007974
Disruption of CXCR2-Mediated MDSC Tumor Trafficking Enhances Anti-PD1 Efficacy
S. Highfill (2014)
Couzin-Frankel J. Cancer immunotherapy. Science
(2013)
10.1158/1535-7163.MCT-11-1014
CTLA-4 Blockade Expands Infiltrating T Cells and Inhibits Cancer Cell Repopulation during the Intervals of Chemotherapy in Murine Mesothelioma
Licun Wu (2012)
10.1158/0008-5472.CAN-13-1545
Doxorubicin eliminates myeloid-derived suppressor cells and enhances the efficacy of adoptive T-cell transfer in breast cancer.
D. Alizadeh (2014)
10.1182/BLOOD-2004-06-2410
Inhibition of CD4(+)25+ T regulatory cell function implicated in enhanced immune response by low-dose cyclophosphamide.
M. E. C. Lutsiak (2005)
10.1038/nm.3045
Dual role of immunomodulation by anticancer chemotherapy
M. Shurin (2013)
Realization of the therapeutic potential of CTLA-4 blockade in low-dose chemotherapy-treated tumor-bearing mice.
M. B. Mokyr (1998)
10.1038/39614
A CD4+T-cell subset inhibits antigen-specific T-cell responses and prevents colitis
H. Groux (1997)
10.1084/JEM.190.10.1417
In Breast Carcinoma Tissue, Immature Dendritic Cells Reside within the Tumor, Whereas Mature Dendritic Cells Are Located in Peritumoral Areas
D. Bell (1999)
10.1182/BLOOD-2006-12-062422
Role of PD-1 and its ligand, B7-H1, in early fate decisions of CD8 T cells.
Monica V. Goldberg (2007)
10.1084/JEM.189.9.1363
Inhibition of  T Cell Proliferation by Macrophage Tryptophan Catabolism
D. Munn (1999)
Association of macrophage infiltration with angiogenesis and prognosis in invasive breast carcinoma.
R. Leek (1996)
10.1084/jem.20050715
Arginase I in myeloid suppressor cells is induced by COX-2 in lung carcinoma
P. Rodriguez (2005)
10.1016/j.ccr.2009.06.017
Polarization of tumor-associated neutrophil phenotype by TGF-beta: "N1" versus "N2" TAN.
Z. Fridlender (2009)
10.1016/j.immuni.2009.04.010
Mechanisms of foxp3+ T regulatory cell-mediated suppression.
E. Shevach (2009)
Chemo-immunotherapy to relieve tumor-induced immunosuppression Frontiers in Immunology | www.frontiersin
Kersten
10.1038/ni904
Foxp3 programs the development and function of CD4+CD25+ regulatory T cells
J. Fontenot (2003)
10.1002/eji.201041093
Efficient Treg depletion induces T‐cell infiltration and rejection of large tumors
X. Li (2010)
10.1186/s12967-014-0376-x
Clinical significance of plasmacytoid dendritic cells and myeloid-derived suppressor cells in melanoma
I. Chevolet (2014)
10.1126/science.1160062
CTLA-4 Control over Foxp3+ Regulatory T Cell Function
K. Wing (2008)
10.1038/nrc1782
Paradoxical roles of the immune system during cancer development
K. E. D. Visser (2006)
10.1056/NEJMoa1200694
Safety and activity of anti-PD-L1 antibody in patients with advanced cancer.
J. Brahmer (2012)
10.1158/0008-5472.CAN-05-1299
Gr-1+CD115+ immature myeloid suppressor cells mediate the development of tumor-induced T regulatory cells and T-cell anergy in tumor-bearing host.
B. Huang (2006)
10.1016/J.IMMUNI.2007.08.014
Granzyme B and perforin are important for regulatory T cell-mediated suppression of tumor clearance.
X. Cao (2007)
10.1016/j.ccr.2010.11.011
Endogenous T cell responses to antigens expressed in lung adenocarcinomas delay malignant tumor progression.
Michel DuPage (2011)
Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases.
S. Sakaguchi (1995)
10.1016/j.ccell.2015.02.015
Macrophages and therapeutic resistance in cancer.
B. Ruffell (2015)
Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer
NA Rizvi (2015)
Balancing immune response: crosstalk between adaptive and innate immune cells during breast cancer progression
D. DeNardo (2007)
10.1165/rcmb.2010-0080OC
Monocyte chemoattractant protein-1 blockade inhibits lung cancer tumor growth by altering macrophage phenotype and activating CD8+ cells.
Z. Fridlender (2011)
10.4049/jimmunol.174.4.1783
Cutting Edge: Contact-Mediated Suppression by CD4+CD25+ Regulatory Cells Involves a Granzyme B-Dependent, Perforin-Independent Mechanism1
David C. Gondek (2005)
10.1158/0008-5472.CAN-06-1278
Macrophages regulate the angiogenic switch in a mouse model of breast cancer.
Elaine Y Lin (2006)
10.1038/nature12477
Signatures of mutational processes in human cancer
L. Alexandrov (2013)
10.2174/1381612043452893
Inhibition of MHC II gene transcription by nitric oxide and antioxidants.
O. Harari (2004)
10.1158/0008-5472.CAN-10-0153
Antiangiogenic agents can increase lymphocyte infiltration into tumor and enhance the effectiveness of adoptive immunotherapy of cancer.
R. Shrimali (2010)
10.1038/nature13954
PD-1 blockade induces responses by inhibiting adaptive immune resistance
P. Tumeh (2014)
10.1172/JCI73639
PD-1 identifies the patient-specific CD8⁺ tumor-reactive repertoire infiltrating human tumors.
A. Gros (2014)
10.1200/JCO.2006.05.9584
Quantification of regulatory T cells enables the identification of high-risk breast cancer patients and those at risk of late relapse.
G. Bates (2006)
10.1097/MOH.0b013e32833eaf1b
High-dose cyclophosphamide for graft-versus-host disease prevention
L. Luznik (2010)
Preoperative neutrophil to lymphocyte ratio as a prognostic predictor after curative resection for non-small cell lung cancer.
M. Tomita (2011)
10.1038/nrc1613
Immunotherapy and chemotherapy — a practical partnership
R. Lake (2005)
10.1016/j.immuni.2013.03.003
Anticancer chemotherapy-induced intratumoral recruitment and differentiation of antigen-presenting cells.
Y. Ma (2013)
PDL1 expression correlates with tumor-infiltrating lymphocytes and response to neoadjuvant chemotherapy in breast cancer
H Wimberly (2015)
10.1158/0008-5472.CAN-13-1550
Therapeutic PD-1 pathway blockade augments with other modalities of immunotherapy T-cell function to prevent immune decline in ovarian cancer.
Jaikumar Duraiswamy (2013)
10.1158/0008-5472.CAN-09-2326
CCL2 blockade augments cancer immunotherapy.
Z. Fridlender (2010)
10.1186/bcr1746
Inflammation and breast cancer. Balancing immune response: crosstalk between adaptive and innate immune cells during breast cancer progression
D. DeNardo (2007)
10.1084/jem.20082492
Blockade of CTLA-4 on both effector and regulatory T cell compartments contributes to the antitumor activity of anti–CTLA-4 antibodies
K. Peggs (2009)
10.1158/0008-5472.CAN-10-0283
Selective depletion of CD4+CD25+Foxp3+ regulatory T cells by low-dose cyclophosphamide is explained by reduced intracellular ATP levels.
Jie Zhao (2010)
10.1038/nm.2028
Activation of the NLRP3 inflammasome in dendritic cells induces IL-1β–dependent adaptive immunity against tumors
F. Ghiringhelli (2009)
10.2307/j.ctvzgb86t.9
Cancer
Zachary Hall (1906)
10.1158/1078-0432.CCR-10-0733
A Novel Chemoimmunomodulating Property of Docetaxel: Suppression of Myeloid-Derived Suppressor Cells in Tumor Bearers
K. Kodumudi (2010)
Immunologic selftolerance maintained by activated T cells expressing IL-2 receptor alphachains (CD25)
S Sakaguchi (1995)
10.1056/NEJMoa1406498
Genetic basis for clinical response to CTLA-4 blockade in melanoma.
A. Snyder (2014)
10.1126/science.aaa1348
Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer
N. Rizvi (2015)
10.1126/scitranslmed.3008918
Anti–CTLA-4 therapy broadens the melanoma-reactive CD8+ T cell response
P. Kvistborg (2014)
Depletion of lymphocyte subpopulations in primary and secondary lymphoid organs of mice by a transplanted granulocytosis-inducing mammary carcinoma.
M. Lee (1982)
10.1007/s00018-013-1286-4
Immune suppression by neutrophils and granulocytic myeloid-derived suppressor cells: similarities and differences
J. Pillay (2013)
J Clin Invest
(2014)
10.1056/NEJMoa1003466
Improved survival with ipilimumab in patients with metastatic melanoma.
F. S. Hodi (2010)
10.1038/nrc3239
The blockade of immune checkpoints in cancer immunotherapy
D. Pardoll (2012)
10.1200/JCO.2014.56.2736
Pooled Analysis of Long-Term Survival Data From Phase II and Phase III Trials of Ipilimumab in Unresectable or Metastatic Melanoma.
D. Schadendorf (2015)
10.1016/j.intimp.2011.12.016
IFN-γ producing T cells contribute to the increase of myeloid derived suppressor cells in tumor-bearing mice after cyclophosphamide treatment.
Q. Guo (2012)
10.1111/j.1440-1711.2005.01371.x
Dendritic cell dysfunction in cancer: A mechanism for immunosuppression
A. Pinzón-Charry (2005)
10.1158/1078-0432.CCR-13-3271
Association of PD-1, PD-1 Ligands, and Other Features of the Tumor Immune Microenvironment with Response to Anti–PD-1 Therapy
J. Taube (2014)
10.1182/BLOOD-2005-02-0642
Reduced frequencies and suppressive function of CD4+CD25hi regulatory T cells in patients with chronic lymphocytic leukemia after therapy with fludarabine.
M. Beyer (2005)
10.1007/s00262-006-0225-8
Metronomic cyclophosphamide regimen selectively depletes CD4+CD25+ regulatory T cells and restores T and NK effector functions in end stage cancer patients
F. Ghiringhelli (2006)
IL-17-producing γδ T cells and neutrophils conspire to promote breast cancer metastasis
(2015)
10.1126/science.342.6165.1432
Breakthrough of the year 2013. Cancer immunotherapy.
J. Couzin-Frankel (2013)
10.1056/NEJMoa1104621
Ipilimumab plus dacarbazine for previously untreated metastatic melanoma.
C. Robert (2011)
10.1056/NEJMoa1414428
Nivolumab and ipilimumab versus ipilimumab in untreated melanoma.
Michael A. Postow (2015)
10.1126/science.aaa4971
Neoantigens in cancer immunotherapy
T. Schumacher (2015)
10.1016/j.immuni.2014.06.008
Macrophage activation and polarization: nomenclature and experimental guidelines.
P. Murray (2014)
10.1158/0008-5472.CAN-09-3690
5-Fluorouracil selectively kills tumor-associated myeloid-derived suppressor cells resulting in enhanced T cell-dependent antitumor immunity.
J. Vincent (2010)
10.4049/jimmunol.164.1.183
Suppressor Effector Function of CD4+CD25+ Immunoregulatory T Cells Is Antigen Nonspecific
A. Thornton (2000)
10.1084/JEM.188.2.287
CD4+CD25+ Immunoregulatory T Cells Suppress Polyclonal T Cell Activation In Vitro by Inhibiting Interleukin 2 Production
A. Thornton (1998)
10.1073/PNAS.75.10.5142
Systemic bacillus Calmette-Guérin (BCG) activates natural suppressor cells.
J. Bennett (1978)
10.1002/cncr.11618
CD4+CD25+ regulatory T cells in patients with gastrointestinal malignancies
T. Sasada (2003)
10.1126/scitranslmed.3003330
CD25 Blockade Depletes and Selectively Reprograms Regulatory T Cells in Concert with Immunotherapy in Cancer Patients
Andrew J. Rech (2012)
Cell interactions in the induction of tolerance: the role of thymic lymphocytes.
R. Gershon (1970)
10.4049/jimmunol.1003460
Regulation of Macrophage Arginase Expression and Tumor Growth by the Ron Receptor Tyrosine Kinase
D. R. Sharda (2011)
10.1158/0008-5472.CAN-09-2587
Myeloid-derived suppressor cells inhibit T-cell activation by depleting cystine and cysteine.
M. Srivastava (2010)
10.1016/j.ccr.2013.01.008
Role of macrophage targeting in the antitumor activity of trabectedin.
G. Germano (2013)
10.1084/JEM.151.1.69
T-cell-mediated suppression of anti-tumor immunity. An explanation for progressive growth of an immunogenic tumor
M. Berendt (1980)
10.1016/j.coi.2015.01.006
The evolution of checkpoint blockade as a cancer therapy: what's here, what's next?
D. Shin (2015)
10.1038/nm.3337
CSF-1R inhibition alters macrophage polarization and blocks glioma progression
S. Pyonteck (2013)
10.1016/J.IMMUNI.2004.09.002
Human T regulatory cells can use the perforin pathway to cause autologous target cell death.
W. Grossman (2004)
10.1016/j.ccr.2012.01.008
Marginating dendritic cells of the tumor microenvironment cross-present tumor antigens and stably engage tumor-specific T cells.
John J. Engelhardt (2012)
10.1016/J.YONC.2012.07.009
Ipilimumab in Combination With Paclitaxel and Carboplatin As First-Line Treatment in Stage IIIB/IV Non–Small-Cell Lung Cancer: Results From a Randomized, Double-Blind, Multicenter Phase II Study
A. Tsao (2012)
10.1084/jem.20082173
Activated monocytes in peritumoral stroma of hepatocellular carcinoma foster immune privilege and disease progression through PD-L1
Dong-Ming Kuang (2009)
10.1158/0008-5472.CAN-08-4102
Cyclophosphamide augments antitumor immunity: studies in an autochthonous prostate cancer model.
S. Wada (2009)
10.1038/nature06306
The inhibitory cytokine IL-35 contributes to regulatory T-cell function
L. Collison (2007)
10.1200/JCO.2012.47.7521
Tumor exome analysis reveals neoantigen-specific T-cell reactivity in an ipilimumab-responsive melanoma.
Nienke van Rooij (2013)
10.1016/j.ccr.2012.02.022
Accessories to the crime: functions of cells recruited to the tumor microenvironment.
D. Hanahan (2012)
10.1007/s00262-012-1388-0
Chemoimmunotherapy: reengineering tumor immunity
Gang Chen (2012)
10.1038/nm1699
Endothelin B receptor mediates the endothelial barrier to T cell homing to tumors and disables immune therapy
R. Buckanovich (2008)
10.1158/0008-5472.CAN-13-3723
CSF1/CSF1R blockade reprograms tumor-infiltrating macrophages and improves response to T-cell checkpoint immunotherapy in pancreatic cancer models.
Y. Zhu (2014)
10.4049/jimmunol.164.2.762
Autocrine Production of IL-10 Mediates Defective IL-12 Production and NF-κB Activation in Tumor-Associated Macrophages1
A. Sica (2000)
10.1056/NEJMoa1302369
Nivolumab plus ipilimumab in advanced melanoma.
J. Wolchok (2013)
10.4049/jimmunol.1201449
Myeloid-Derived Suppressor Cells Suppress Antitumor Immune Responses through IDO Expression and Correlate with Lymph Node Metastasis in Patients with Breast Cancer
Jinpu Yu (2013)
10.3389/fimmu.2015.00187
Combinatorial Strategies for the Induction of Immunogenic Cell Death
L. Bezu (2015)
10.1084/jem.20062512
Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression
S. Deaglio (2007)
10.1007/s10549-011-1799-1
Prognostic value of chemotherapy-induced neutropenia in early-stage breast cancer
Yunwei Han (2011)
10.1158/0008-5472.CAN-06-3037
The terminology issue for myeloid-derived suppressor cells.
D. Gabrilovich (2007)
10.1038/nrc3237
Combining immunotherapy and targeted therapies in cancer treatment
M. Vanneman (2012)
10.1016/j.it.2015.02.006
Immune-mediated mechanisms influencing the efficacy of anticancer therapies.
S. Coffelt (2015)
10.1016/j.cell.2014.12.033
Molecular and Genetic Properties of Tumors Associated with Local Immune Cytolytic Activity
M. Rooney (2015)
10.1084/jem.20101956
Chemokine nitration prevents intratumoral infiltration of antigen-specific T cells
B. Molon (2011)
10.1182/blood-2010-12-325753
A human promyelocytic-like population is responsible for the immune suppression mediated by myeloid-derived suppressor cells.
S. Solito (2011)
10.1177/0300060514561504
Suppressive effects of gemcitabine plus cisplatin chemotherapy on regulatory T cells in nonsmall-cell lung cancer
C. Chen (2015)
10.1371/journal.pone.0061895
Synergistic Effect of CTLA-4 Blockade and Cancer Chemotherapy in the Induction of Anti-Tumor Immunity
W. Lesterhuis (2013)
10.1084/jem.20130579
Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti–CTLA-4 therapy against melanoma
Tyler R. Simpson (2013)
10.4048/jbc.2013.16.1.55
Usefulness of Pretreatment Neutrophil to Lymphocyte Ratio in Predicting Disease-Specific Survival in Breast Cancer Patients
Hany Noh (2013)
10.1002/ijc.27990
Low‐dose gemcitabine depletes regulatory T cells and improves survival in the orthotopic Panc02 model of pancreatic cancer
Ivan Shevchenko (2013)
10.1158/1078-0432.CCR-05-0883
Gemcitabine Selectively Eliminates Splenic Gr-1+/CD11b+ Myeloid Suppressor Cells in Tumor-Bearing Animals and Enhances Antitumor Immune Activity
E. Suzuki (2005)
10.1007/s00262-008-0523-4
Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin–cyclophosphamide chemotherapy
C. Diaz-Montero (2008)
10.1038/nature13904
MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer
T. Powles (2014)
10.1038/nature04444
Restoring function in exhausted CD8 T cells during chronic viral infection
D. Barber (2006)
10.1038/jid.2012.444
Cyclophosphamide promotes chronic inflammation-dependent immunosuppression and prevents antitumor response in melanoma.
A. Sevko (2013)
10.1016/j.celrep.2012.08.006
Immune tolerance to tumor antigens occurs in a specialized environment of the spleen.
S. Ugel (2012)
10.1038/nature13988
Checkpoint Blockade Cancer Immunotherapy Targets Tumour-Specific Mutant Antigens
M. M. Gubin (2014)
10.1158/0008-5472.CAN-12-4100
Dual blockade of PD-1 and CTLA-4 combined with tumor vaccine effectively restores T-cell rejection function in tumors.
Jaikumar Duraiswamy (2013)
10.1016/j.ccr.2011.08.012
Tumor entrained neutrophils inhibit seeding in the premetastatic lung.
Z. Granot (2011)
10.1038/nrc1369
The anti-angiogenic basis of metronomic chemotherapy
R. Kerbel (2004)
High-dose cyclophosphamide for graft-versushost disease prevention
L Luznik (2010)
10.3892/OR.16.1.141
Different mechanisms for anti-tumor effects of low- and high-dose cyclophosphamide.
Y. Motoyoshi (2006)
10.1371/journal.pone.0076379
Tumor Secretion of CCL22 Activates Intratumoral Treg Infiltration and Is Independent Prognostic Predictor of Breast Cancer
Y. Li (2013)
10.1158/2159-8274.CD-10-0028
Leukocyte complexity predicts breast cancer survival and functionally regulates response to chemotherapy.
D. DeNardo (2011)
10.1016/0959-8049(95)00172-F
Thymidylate synthase and drug resistance.
G. Peters (1995)
10.1186/1479-5876-6-12
Transient T cell depletion causes regression of melanoma metastases
M. A. Rasku (2008)
10.1016/j.intimp.2009.03.015
Gemcitabine directly inhibits myeloid derived suppressor cells in BALB/c mice bearing 4T1 mammary carcinoma and augments expansion of T cells from tumor-bearing mice.
Hanh K. Le (2009)
10.1016/j.bbmt.2008.03.005
HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide.
L. Luznik (2008)
Production of colony-stimulating factor by tumor cells and the factor-mediated induction of suppressor cells.
Y. Tsuchiya (1988)
10.1007/s00262-011-1046-y
Prognostic role of FOXP3+ regulatory T cells infiltrating human carcinomas: the paradox of colorectal cancer
S. Ladoire (2011)
10.1016/j.celrep.2014.12.039
Phenotypic diversity and plasticity in circulating neutrophil subpopulations in cancer.
J. Y. Sagiv (2015)
10.1073/pnas.1424927112
Invasive breast cancer reprograms early myeloid differentiation in the bone marrow to generate immunosuppressive neutrophils
Amy-Jo Casbon (2015)
10.1158/0008-5472.CAN-04-0757
High-Dose Granulocyte-Macrophage Colony-Stimulating Factor-Producing Vaccines Impair the Immune Response through the Recruitment of Myeloid Suppressor Cells
P. Serafini (2004)
10.3389/fimmu.2013.00190
Natural and Induced T Regulatory Cells in Cancer
Dennis O. Adeegbe (2013)
10.1016/j.ccell.2015.03.001
Immune checkpoint blockade: a common denominator approach to cancer therapy.
S. Topalian (2015)
10.1371/journal.pone.0027690
Tumor-Derived G-CSF Facilitates Neoplastic Growth through a Granulocytic Myeloid-Derived Suppressor Cell-Dependent Mechanism
J. D. Waight (2011)
10.1126/science.1171362
Inhibition of Hedgehog Signaling Enhances Delivery of Chemotherapy in a Mouse Model of Pancreatic Cancer
K. Olive (2009)
10.1158/2159-8290.CD-14-0863
The vigorous immune microenvironment of microsatellite instable colon cancer is balanced by multiple counter-inhibitory checkpoints.
Nicolas J. Llosa (2015)
10.1002/pros.22858
Breaking immune tolerance by targeting CD25+ regulatory T cells is essential for the anti‐tumor effect of the CTLA‐4 blockade in an HLA‐DR transgenic mouse model of prostate cancer
E. Klyushnenkova (2014)
10.1016/j.immuni.2014.01.006
Transcriptome-Based Network Analysis Reveals a Spectrum Model of Human Macrophage Activation
Jia Xue (2014)
10.1038/nature14011
Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients
R. Herbst (2014)
10.1038/nm1523
Calreticulin exposure dictates the immunogenicity of cancer cell death
M. Obeid (2007)
10.1038/nm863
Blockade of B7-H1 improves myeloid dendritic cell–mediated antitumor immunity
T. Curiel (2003)
10.1093/annonc/mdv192
PD-L1 protein expression in breast cancer is rare, enriched in basal-like tumours and associated with infiltrating lymphocytes.
H. R. Ali (2015)
10.1016/J.IT.2004.09.015
The chemokine system in diverse forms of macrophage activation and polarization.
A. Mantovani (2004)
10.1371/journal.pone.0094376
Prognostic Value of Tumor-Infiltrating FoxP3+ T Cells in Gastrointestinal Cancers: A Meta Analysis
Y. Huang (2014)
10.1002/ijc.27801
Immunomodulatory effects of low dose chemotherapy and perspectives of its combination with immunotherapy
M. S. Nars (2013)
10.1200/JCO.2006.09.4565
Intratumoral balance of regulatory and cytotoxic T cells is associated with prognosis of hepatocellular carcinoma after resection.
Q. Gao (2007)
10.1158/0008-5472.CAN-12-0210
Radiotherapy increases the permissiveness of established mammary tumors to rejection by immunomodulatory antibodies.
I. Verbrugge (2012)



This paper is referenced by
10.3389/fimmu.2018.02100
The Antitumor Activity of Combinations of Cytotoxic Chemotherapy and Immune Checkpoint Inhibitors Is Model-Dependent
Chloé Grasselly (2018)
10.1016/j.intimp.2019.106006
Gemcitabine enhances cytotoxic activity of effector T-lymphocytes against chemo-resistant cholangiocarcinoma cells.
N. Sawasdee (2019)
10.1002/ptr.5781
Traditional Oriental Herbal Medicine and Natural Killer Cells for Cancer Patients: A Systematic Review and Meta‐analysis
K. Bae (2017)
10.1007/s00262-020-02696-4
The impact of ICOS+ regulatory T cells and Helicobacter pylori infection on the prognosis of patients with gastric and colorectal cancer: potential prognostic benefit of pre-operative eradication therapy
Shinya Urakawa (2020)
10.1016/j.nano.2016.12.005
Fluorescent nanodiamonds engage innate immune effector cells: A potential vehicle for targeted anti-tumor immunotherapy.
L. Suarez-Kelly (2017)
10.2217/BMT-2017-0014
Towards predictive biomarkers for immunotherapy response in breast cancer patients
Leonie Voorwerk (2018)
Un néolymphocyte T pour une thérapie médicamenteuse de demain : « espoir ou réalité »
Quentin Gardan (2017)
10.1038/s41375-018-0062-8
Histone deacetylase (HDAC) inhibitor ACY241 enhances anti-tumor activities of antigen-specific central memory cytotoxic T lymphocytes against multiple myeloma and solid tumors
J. Bae (2018)
10.1053/j.gastro.2016.06.032
Gemcitabine Activates Natural Killer Cells to Attenuate Pancreatic Cancer Recurrence.
D. Dawson (2016)
10.18632/oncotarget.18202
Preclinical data on the combination of cisplatin and anti-CD70 therapy in non-small cell lung cancer as an excellent match in the era of combination therapy
J. Jacobs (2017)
10.2217/fon-2019-0542
Is there a role for maintenance therapy after platinum chemotherapy in bladder cancer in the era of immune therapy?
E. Rassy (2019)
10.1016/j.it.2017.05.006
Integrating Next-Generation Dendritic Cell Vaccines into the Current Cancer Immunotherapy Landscape.
Abhishek D Garg (2017)
10.1016/j.matcom.2020.11.014
Extinction and persistence of a tumor-immune model with white noise and pulsed comprehensive therapy
H. Yang (2021)
10.1016/j.omto.2019.03.007
Enhancing Dendritic Cell Therapy in Solid Tumors with Immunomodulating Conventional Treatment
Robert A. Belderbos (2019)
10.1007/s11864-020-00790-4
The Potential of Immune Checkpoint Blockade in Cervical Cancer: Can Combinatorial Regimens Maximize Response? A Review of the Literature
Lennox Chitsike (2020)
10.1016/j.biomaterials.2020.119928
Quantum dot-pulsed dendritic cell vaccines plus macrophage polarization for amplified cancer immunotherapy.
F. Liu (2020)
10.1111/imr.12574
Cell death and immunity in cancer: From danger signals to mimicry of pathogen defense responses
Abhishek D Garg (2017)
10.1080/2162402X.2019.1703449
Trial watch: chemotherapy-induced immunogenic cell death in immuno-oncology
Isaure Vanmeerbeek (2020)
10.18632/oncotarget.18202
Preclinical data on the combination of cisplatin and anti-CD70 therapy in non-small cell lung cancer as an excellent match in the era of combination therapy.
J. Jacobs (2017)
10.3892/ol.2017.5721
Harnessing antitumor immunity: Employment of tumor recall antigens to optimize the inflammatory response to cancer
Kimberly Silverio (2017)
10.1007/978-3-319-46906-5
Interleukin 12: Antitumor Activity and Immunotherapeutic Potential in Oncology
W. Lasek (2016)
Établissement et caractérisation de modèles précliniques de résistance aux inhibiteurs de points de contrôles immunitaires
Chloé Grasselly (2018)
10.1080/14712598.2019.1571036
Immunotherapy alone or chemo-immunotherapy as front-line treatment for advanced non-small cell lung cancer
Michael Shafique (2019)
10.1007/s11864-018-0556-7
Immune Checkpoint Inhibitors in Early-Stage and Locally Advanced Non-Small Cell Lung Cancer
Sonam Puri (2018)
10.1158/0008-5472.CAN-19-3981
Searching for Goldilocks: How Evolution and Ecology Can Help Uncover More Effective Patient-Specific Chemotherapies
D. Park (2020)
10.1016/j.ijpharm.2020.119787
Induction of Immunogenic Cell Death of Cancer Cells through Nanoparticle-Mediated Dual Chemotherapy and Photothermal Therapy.
Niloofar Heshmati Aghda (2020)
10.1016/j.intimp.2017.04.003
IFN&ggr; enhances cytotoxic efficiency of the cytotoxic T lymphocytes against human glioma cells
Shengwen Shao (2017)
10.1016/BS.IRCMB.2019.06.001
Type I interferons and dendritic cells in cancer immunotherapy.
Jenny Sprooten (2019)
10.1016/j.lungcan.2017.01.007
Phase I/II study of tecemotide as immunotherapy in Japanese patients with unresectable stage III non-small cell lung cancer.
N. Katakami (2017)
10.4049/jimmunol.1900930
Tumor Microenvironment following Gemcitabine Treatment Favors Differentiation of Immunosuppressive Ly6Chigh Myeloid Cells
Caijun Wu (2020)
10.1002/ijc.31842
Rapalog combined with CCR4 antagonist improves anticancer vaccines efficacy
Laurent Beziaud (2018)
10.1016/j.semcdb.2016.09.008
Roles of immune microenvironment heterogeneity in therapy-associated biomarkers in lung cancer.
L. Wang (2017)
See more
Semantic Scholar Logo Some data provided by SemanticScholar