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Emerging Immunotherapy Targets In Lung Cancer

Hao-Hua Zhu, Y. Feng, X. Hu
Published 2020 · Medicine

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Abstract Immunotherapy has become the mainstay for lung cancer treatment, providing sustained therapeutic responses and improved prognosis compared with those obtained with surgery, chemotherapy, radiotherapy, and targeted therapy. It has the potential for anti-tumor treatment and killing tumor cells by activating human immunity and has moved the targets of anti-cancer therapy from malignant tumor cells to immune cell subsets. Two kinds of immune checkpoints, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1), are the main targets of current immunotherapy in lung cancer. Despite the successful outcomes achieved by immune checkpoint inhibitors, a small portion of lung cancer patients remain unresponsive to checkpoint immunotherapy or may ultimately become resistant to these agents as a result of the complex immune modulatory network in the tumor microenvironment. Therefore, it is imperative to exploit novel immunotherapy targets to further expand the proportion of patients benefiting from immunotherapy. This review summarizes the molecular features, biological function, and clinical significance of several novel checkpoints that have important roles in lung cancer immune responses beyond the CTLA-4 and PD-1/PD-L1 axes, including the markers of co-inhibitory and co-stimulatory T lymphocyte pathways and inhibitory markers of macrophages and natural killer cells.
This paper references
10.1186/1479-5876-8-71
First-line chemoimmunotherapy in metastatic breast carcinoma: combination of paclitaxel and IMP321 (LAG-3Ig) enhances immune responses and antitumor activity
C. Brignone (2010)
CD 47-blocking immunotherapies stimulate macrophage-mediated destruction of small-cell lung cancer
K. Weiskopf (2016)
10.1016/j.it.2017.12.001
Natural Killer Cell Education and the Response to Infection and Cancer Therapy: Stay Tuned.
Jeanette E Boudreau (2018)
10.1016/j.ccell.2017.11.001
Antibody Tumor Targeting Is Enhanced by CD27 Agonists through Myeloid Recruitment
A. H. Turaj (2017)
Targeting CD 47 and autophagy elicited enhanced antitumor effects in non - small cell lung cancer
X Zhang (2017)
10.1016/j.ejca.2018.06.020
Indoleamine 2,3-dioxygenase 1 and programmed cell death-ligand 1 co-expression correlates with aggressive features in lung adenocarcinoma.
Y. Kozuma (2018)
10.1038/s41598-017-06410-w
Programmed death one homolog maintains the pool size of regulatory T cells by promoting their differentiation and stability
Qi Wang (2017)
10.1111/imr.12525
Immunoregulatory functions of VISTA
Elizabeth Nowak (2017)
10.1158/1078-0432.CCR-17-2924
Wide Expression and Significance of Alternative Immune Checkpoint Molecules, B7x and HHLA2, in PD-L1–Negative Human Lung Cancers
H. Cheng (2018)
10.1038/ni0303-295
Lethal T cell immunodeficiency induced by chronic costimulation via CD27-CD70 interactions
K. Tesselaar (2003)
10.1186/s12967-018-1595-3
Can IDO activity predict primary resistance to anti-PD-1 treatment in NSCLC?
A. Botticelli (2018)
10.1172/JCI74589
Coinhibitory receptor PD-1H preferentially suppresses CD4⁺ T cell-mediated immunity.
D. Flies (2014)
10.1200/JCO.2017.75.3384
Molecular Determinants of Response to Anti-Programmed Cell Death (PD)-1 and Anti-Programmed Death-Ligand 1 (PD-L1) Blockade in Patients With Non-Small-Cell Lung Cancer Profiled With Targeted Next-Generation Sequencing.
H. Rizvi (2018)
10.1111/imr.12520
Tim‐3 and its role in regulating anti‐tumor immunity
M. Das (2017)
10.1038/ni1271
The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity
C. Zhu (2005)
Indoleamine 2 , 3 - dioxygenase 1 inhibition targets anti - PD 1 - resistant lung tumors by blocking myeloid - derived suppressor cells
A Li (2018)
10.1038/s41590-018-0132-0
Blockade of the checkpoint receptor TIGIT prevents NK cell exhaustion and elicits potent anti-tumor immunity
Q. Zhang (2018)
10.1158/1078-0432.CCR-17-2852
B7-H3 Negatively Modulates CTL-Mediated Cancer Immunity
K. Yonesaka (2018)
B 7 - H 7 ( HHLA 2 ) inhibits T - cell activation and proliferation in the presence of TCR and CD 28 signaling
H Cheng
10.1016/j.cell.2018.11.010
Fibrinogen-like Protein 1 Is a Major Immune Inhibitory Ligand of LAG-3
J. Wang (2019)
10.1159/000453175
Astragaloside IV Enhances Cisplatin Chemosensitivity in Non-Small Cell Lung Cancer Cells Through Inhibition of B7-H3
C. He (2016)
Roles of LAG 3 and EGR 2 in regulatory T cells
T Okamura (2012)
10.1172/JCI81187
TIGIT predominantly regulates the immune response via regulatory T cells.
S. Kurtuluş (2015)
10.1038/nm.4308
VISTA is an inhibitory immune checkpoint that is increased after ipilimumab therapy in patients with prostate cancer
Jianjun Gao (2017)
PD-1 ef fi ciently inhibits T cell activation even in the presence of co-stimulation through CD 27 and GITR
Reina Mizuno (2019)
10.4161/2162402X.2014.992237
GITR agonist enhances vaccination responses in lung cancer
L. Zhu (2015)
10.1038/s41586-019-1674-5
VISTA is an acidic pH-selective ligand for PSGL-1
Robert J. Johnston (2019)
10.1111/j.1365-2567.2011.03415.x
Increased killer immunoglobulin‐like receptor expression and functional defects in natural killer cells in lung cancer
S. A. Al Omar (2011)
10.1016/j.lungcan.2018.06.028
Case-control study of PD-1, PD-L1 and B7-H3 expression in lung cancer patients with and without human immunodeficiency virus (HIV) infection.
K. Scilla (2018)
10.1038/nri2526
The role of TNF superfamily members in T-cell function and diseases
M. Croft (2009)
10.1080/19420862.2019.1629239
Characterization of a novel anti-human lymphocyte activation gene 3 (LAG-3) antibody for cancer immunotherapy
Xiaojie Yu (2019)
patients with and without human immunode fi ciency virus ( HIV ) infection
D Luo (2018)
HHLA 2 and TMIGD 2 : new immunotherapeutic targets of the B 7 and CD 28 families
M. Janakiram (2015)
10.1038/ni967
The B7 family member B7-H3 preferentially down-regulates T helper type 1–mediated immune responses
Woong-Kyung Suh (2003)
10.1111/imm.13001
VSIG‐3 as a ligand of VISTA inhibits human T‐cell function
J. Wang (2019)
10.18632/oncotarget.9899
CD47 deficiency in tumor stroma promotes tumor progression by enhancing angiogenesis
L. Gao (2017)
HHLA 2 is a member of the B 7 family and inhibits human CD 4 and CD 8 T - cell function
M Janakiram (2013)
10.1016/j.intimp.2015.09.017
Increased Tim-3 expression in peripheral NK cells predicts a poorer prognosis and Tim-3 blockade improves NK cell-mediated cytotoxicity in human lung adenocarcinoma.
L. Xu (2015)
10.1158/1078-0432.CCR-15-3071
HHLA2, a New Immune Checkpoint Member of the B7 Family, Is Widely Expressed in Human Lung Cancer and Associated with EGFR Mutational Status
H. Cheng (2016)
10.1016/j.lungcan.2018.12.008
Co-expression of IDO1 and PD-L1 in lung squamous cell carcinoma: Potential targets of novel combination therapy.
K. Takada (2019)
10.1158/1078-0432.CCR-17-2542
Spatially Resolved and Quantitative Analysis of VISTA/PD-1H as a Novel Immunotherapy Target in Human Non–Small Cell Lung Cancer
F. Villarroel‐Espíndola (2017)
10.1111/imr.12527
The CD47‐SIRPα signaling axis as an innate immune checkpoint in cancer
Hanke L. Matlung (2017)
10.1158/0008-5472.CAN-17-2995
IDO Immune Status after Chemoradiation May Predict Survival in Lung Cancer Patients.
Weili Wang (2018)
10.2147/DDDT.S163304
The combination of anti-KIR monoclonal antibodies with anti-PD-1/PD-L1 monoclonal antibodies could be a critical breakthrough in overcoming tumor immune escape in NSCLC
Y. He (2018)
10.1016/j.cllc.2017.12.001
LAG‐3 in Non–Small‐cell Lung Cancer: Expression in Primary Tumors and Metastatic Lymph Nodes Is Associated With Improved Survival
S. Hald (2018)
10.1200/JCO.2016.70.1508
Safety and Activity of Varlilumab, a Novel and First-in-Class Agonist Anti-CD27 Antibody, in Patients With Advanced Solid Tumors.
H. Burris (2017)
B 7 - H 3 expression in NSCLC and its association with B 7 - H 4 , PD - L 1 and tumor - in fi ltrating lymphocytes
M Altan (2017)
CD 27 - mediated regulatory T cell depletion and effector T cell costimulation both contribute to antitumor ef fi cacy
A Wasiuk (2017)
The B 7 family member B 7 - H 3 preferentially down - 1 H ) expression and function in normal and HIV infected individuals
WK Suh (2014)
10.1016/j.jtho.2017.01.019
LAG‐3 Protein Expression in Non–Small Cell Lung Cancer and Its Relationship with PD‐1/PD‐L1 and Tumor‐Infiltrating Lymphocytes
Y. He (2017)
10.1084/JEM.171.5.1393
LAG-3, a novel lymphocyte activation gene closely related to CD4
F. Triebel (1990)
10.1038/s41590-018-0217-9
LAG-3 inhibits the activation of CD4+ T cells that recognize stable pMHCII through its conformation-dependent recognition of pMHCII
Takumi Maruhashi (2018)
Induced expression of B 7 - H 3 on the lung cancer cells and macrophages suppresses T - cell mediating anti - tumor immune response
C Chen (2013)
10.1016/j.celrep.2019.03.004
Lymphocyte Activation Gene-3 Maintains Mitochondrial and Metabolic Quiescence in Naive CD4+ T Cells.
Dana M Previte (2019)
10.1002/ijc.32951
Phase 1 study of epacadostat in combination with atezolizumab for patients with previously treated advanced nonsmall cell lung cancer
M. Hellmann (2020)
10.1016/j.it.2016.01.002
IDO in the Tumor Microenvironment: Inflammation, Counter-Regulation, and Tolerance.
D. Munn (2016)
Expression pro fi les and clinical value of plasma exosomal Tim - 3 and Galectin - 9 in non - small cell lung cancer
J Gao (2018)
10.1111/imr.12518
TIGIT and CD96: new checkpoint receptor targets for cancer immunotherapy
W. Dougall (2017)
10.1186/s12885-018-4990-5
Immunotherapy for non-small cell lung cancers: biomarkers for predicting responses and strategies to overcome resistance
X. Pu (2018)
Lymphocyteactivation gene 3/major histocompatibility complex class II interaction modulates the antigenic response of CD4+ T lymphocytes
B Huard (1994)
KIR 2 D ( L 1 , L 3 , L 4 , S 4 ) and KIR 3 DL 1 protein expression in non - small cell lung cancer
Y He (2016)
10.1084/jem.20100619
VISTA, a novel mouse Ig superfamily ligand that negatively regulates T cell responses
L. Wang (2011)
10.3389/fimmu.2018.02170
Anti-glucocorticoid-induced Tumor Necrosis Factor–Related Protein (GITR) Therapy Overcomes Radiation-Induced Treg Immunosuppression and Drives Abscopal Effects
Jonathan E Schoenhals (2018)
10.1084/jem.20100643
Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity
Kaori Sakuishi (2010)
10.1016/j.cell.2018.09.035
A Paradigm Shift in Cancer Immunotherapy: From Enhancement to Normalization
M. Sanmamed (2018)
10.1159/000502441
High Serum Soluble CD27 Level Correlates with Poor Performance Status and Reduced Survival in Patients with Advanced Lung Cancer
J. Kashima (2019)
10.1080/14728222.2018.1512588
Glucocorticoid-induced TNFR-related gene (GITR) as a therapeutic target for immunotherapy
C. Riccardi (2018)
CD 47 promotes tumor invasion and metastasis in non - small cell lung cancer
H Zhao (2016)
10.3389/fimmu.2019.01573
Prognostic Significance of Potential Immune Checkpoint Member HHLA2 in Human Tumors: A Comprehensive Analysis
B. Wang (2019)
10.1016/J.IMMUNI.2004.08.010
Role of LAG-3 in regulatory T cells.
C. Huang (2004)
10.1186/s13046-019-1266-0
Advances in cancer immunotherapy 2019 – latest trends
S. Kruger (2019)
10.1016/j.jcyt.2018.05.002
Dual Effect of Glucocorticoid-Induced Tumor Necrosis Factor-Related Receptor Ligand Carrying Mesenchymal Stromal Cells on Small Cell Lung Cancer: A Preliminary in vitro Study.
C. Z. Kopru (2018)
10.1038/s41591-019-0420-8
Rational design of anti-GITR-based combination immunotherapy
R. Zappasodi (2019)
B 7-H 5 costimulates human T cells via CD 28 H
Yuwen Zhu (2013)
10.1016/j.cca.2016.04.009
Upregulation of soluble B7-H3 in NSCLC-derived malignant pleural effusion: A potential diagnostic biomarker correlated with NSCLC staging.
L. Chen (2016)
10.3389/fimmu.2018.02145
Durable Clinical Responses and Long-Term Follow-Up of Stage III–IV Non-Small-Cell Lung Cancer (NSCLC) Patients Treated With IDO Peptide Vaccine in a Phase I Study—A Brief Research Report
J. W. Kjeldsen (2018)
10.1371/journal.pone.0030676
TIM-3 Expression Characterizes Regulatory T Cells in Tumor Tissues and Is Associated with Lung Cancer Progression
X. Gao (2012)
10.1111/imr.12316
Human KIR repertoires: shaped by genetic diversity and evolution
Angela R. Manser (2015)
10.1021/acs.molpharmaceut.8b00076
A Glutamine-Rich Carrier Efficiently Delivers Anti-CD47 siRNA Driven by a "Glutamine Trap" To Inhibit Lung Cancer Cell Growth.
J. Wu (2018)
Emerging immunotherapy targets in lung cancer
H H Zhu (2020)
CD 47 over - expression is associated with decreased neutrophil apoptosis / phagocytosis and poor prognosis in non - small - cell lung cancer patients
L Barrera (2017)
10.1016/j.ccell.2014.10.018
The immunoreceptor TIGIT regulates antitumor and antiviral CD8(+) T cell effector function.
Robert J. Johnston (2014)
10.1073/PNAS.94.11.5744
Characterization of the major histocompatibility complex class II binding site on LAG-3 protein.
B. Huard (1997)
10.1158/1535-7163.MCT-18-0836
TSR-033, a Novel Therapeutic Antibody Targeting LAG-3, Enhances T-Cell Function and the Activity of PD-1 Blockade In Vitro and In Vivo
Srimoyee Ghosh (2018)
10.1038/modpathol.2017.89
Negative immune checkpoint regulation by VISTA: a mechanism of acquired resistance to anti-PD-1 therapy in metastatic melanoma patients
H. Kakavand (2017)
10.1016/J.MOLMED.2005.06.008
The TIM gene family regulates autoimmune and allergic diseases.
J. H. Meyers (2005)
Non - small cell lung cancer induces an immunosuppressive phenotype of dendritic cells in tumor microenvironment by upregulating B 7 - H 3
T Schneider (2011)
The third group of the B 7 - CD 28 immune checkpoint family : HHLA 2 , TMIGD 2 , B 7 x , and B 7 - H 3
M Janakiram (2017)
10.1021/acs.molpharmaceut.8b00997
Enhancing Anti-PD-1/PD-L1 Immune Checkpoint Inhibitory Cancer Therapy by CD276-Targeted Photodynamic Ablation of Tumor Cells and Tumor Vasculature.
Rui Bao (2019)
10.1001/jamanetworkopen.2019.2535
Estimation of the Percentage of US Patients With Cancer Who Are Eligible for and Respond to Checkpoint Inhibitor Immunotherapy Drugs
A. Haslam (2019)
10.1371/journal.pone.0109103
Characterization of Programmed Death-1 Homologue-1 (PD-1H) Expression and Function in Normal and HIV Infected Individuals
P. Bharaj (2014)
10.3322/caac.21492
Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries
F. Bray (2018)
10.1158/2159-8290.CD-15-0944
Suppression of Metastases Using a New Lymphocyte Checkpoint Target for Cancer Immunotherapy.
S. Blake (2016)
10.1038/ncomms10501
Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints
S. Koyama (2016)
B7-H3: a costimulatory molecule for T cell activation and IFN-gamma production.
A. Chapoval (2001)
10.1016/j.bbrc.2016.12.021
B7-H3 regulates lipid metabolism of lung cancer through SREBP1-mediated expression of FASN.
D. Luo (2017)
Case - control study of PD - 1 , PD - L 1 and B 7 - H 3 expression in
KA Scilla
10.1016/j.lungcan.2018.04.009
Characterization of TIM-3 expression and its prognostic value in patients with surgically resected lung adenocarcinoma.
H. Su (2018)



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