Immunosurveillance and Immunoediting of Lung Cancer: Current Perspectives and Challenges
Abstract
1. Introduction
2. Cancer-Immunity Cycle
2.1. Cancer-Immunity Cycle Outlined
2.2. CD8-Positive Cytotoxic T Cells
2.3. CD28 Family: Cytotoxic T-lymphocyte Associated Protein 4 and Programmed Cell Death 1
2.4. TNF Receptor Superfamily: OX-40 and Glucocorticoid-Induced TNFR-Related (GITR) Gene
3. Tumors Escape Immunosurveillance through Immunoediting
4. Human Leukocyte Antigen (HLA) Loss and Immune Escape in Lung Cancer Evolution
5. Heterogenous Immunoediting in Lung Cancer
6. Neoantigen Derived from Mutation
6.1. Tumor Antigens
6.2. Anti-Tumor Immune Responses by Neoantigen-Specific T Cells
7. Treg and Tumor Immunity
8. Tumor-Associated Macrophages (TAMs) and Tumor Immunity
9. Methods of Overcoming Tumor Immunoediting
9.1. Success of Immune Checkpoint Inhibitors in NSCLC Patients
9.2. Treg-Targeting Treatment
9.3. TAM-Targeting Cancer Treatment
9.4. Phagocytosis Checkpoint Inhibitors
9.5. Cancer Vaccines
9.6. Chimeric Antigen Receptor T Cell and Bispecific Antibodies for Lung Cancer
10. Future Perspective
11. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
MHC I | Major histocompatibility complex class I |
PD-L1 | Programmed cell death ligand 1 |
CTLA-4 | Cytotoxic T-lymphocyte associated protein 4 |
NK | Natural killer |
HLA | Human leukocyte antigen |
LOH | Loss of heterozygosity |
NSCLCs | Non-small-cell lung cancers |
TCGA | The Cancer Genome Atlas |
TRACERx | TRAcking Cancer Evolution through Therapy (Rx) |
TCR | T cell antigen receptor |
ICIs | Immune checkpoint inhibitors |
Ig | Immunoglobulin |
OS | Overall survival |
PFS | Progression-free survival |
TMB | Tumor mutation burden |
APCs | Antigen-presenting cells |
CD47-SIRPα | CD47-signal-regulatory protein α |
DCs | Dendritic cells |
FLT3L | FMS-like tyrosine kinase 3 ligand |
TGFβ | Transforming growth factor- β |
CCL | CC-chemokine ligand |
VEGF | Vascular endothelial growth factor |
NY-ESO-1 | New York esophageal squamous cell carcinoma 1 |
TILs | Tumor-infiltrating lymphocytes |
CAR | Chimeric antigen receptor |
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Co-Stimulatory Molecule | Ligand | Expression on Teff | Effects on Teff Function | Expression on Treg | Effects on Treg Function |
---|---|---|---|---|---|
CTLA-4 | CD80, CD86 | induced by stimulation | ↓ | constitutively expressed | ↑ |
PD-1 | PD-L1 | induced by stimulation | ↓ | constitutively expressed | ↑ |
ICOS | ICOSL | induced by stimulation | ↑ | constitutively expressed | ↑ |
TIGIT | CD155 | induced by stimulation | ↓ | constitutively expressed | ↑ |
CD27 | CD70 | constitutively expressed | ↑ | constitutively expressed | ↑ |
4-1BB | 4-1BBL | induced by stimulation | ↑ | - | - |
OX40 | OX40L | induced by stimulation | ↑ | constitutively expressed | ↓ |
GITR | GITRL | induced by stimulation | ↑ | constitutively expressed | ↓ |
CD226 | CD155 | constitutively expressed | ↑ | - | - |
BTLA | HVEM | constitutively expressed | ↓ | - | - |
TIM-3 | galectin-9 | induced by stimulation | ↓ | constitutively expressed | ↑ |
LAG-3 | MHC-II | induced by stimulation | ↓ | induced by stimulation | ↑ |
Clinical Trials, Gov Identifier | Phase | Intervention | Trial Design | Cancer Type | Primary End Points |
---|---|---|---|---|---|
Monotherapy Trials | |||||
NCT03763149 | I | Anti-CD47 antibody (IBI188) | Dose escalation | advanced malignancies and lymphoma | safety and tolerability |
NCT02678338 | I | Anti-CD47 antibody (Hu5F9-G4) | Dose escalation | hematological malignancies | tolerability |
NCT02216409 | I | Anti-CD47 antibody (Hu5F9-G4) | Dose escalation | solid tumors | safety and tolerability |
NCT03834948 | I | Anti-CD47 antibody (AO-176) | Dose escalation Dose expansion | solid tumors | safety and tolerability |
NCT03013218 | I | high-affinity SIRPα fusion protein (ALX148) | Dose escalation | solid tumors and lymphoma | dose-limiting toxicity |
NCT03512340 | I | Anti-CD47 antibody (SRF231) | Dose escalation Dose expansion | solid tumors hematological malignancies | safety and tolerability |
Combination Trials | |||||
NCT02367196 | I | Anti-CD47 antibody (CC-90002) alone or in combination with rituximab | Dose escalation | solid tumors and hematological malignancies | safety and tolerability |
NCT02663518 | I | SIRPαFc (TTI-621) alone or in combination with rituximab or nivolumab | Dose escalation | relapsed/refractory hematological and solid malignancies | safety and tolerability |
NCT02890368 | I | SIRPαFc (TTI-621) alone or in combination with an anti-PD-1/PD-L1 agent, pegylated IFNα2a, T-VEC or radiation | non-randomized parallel assignment | solid tumors and mycosis fungoides | optimal delivery regimen |
NCT03248479 | Ib | Anti-CD47 antibody (Hu5F9-G4) alone or in combination with azactidine | non-randomized | AML and MDS | safety and tolerability |
NCT02953509 | Ib/II | Anti-CD47 antibody (Hu5F9-G4) in combination with rituximab | single-arm, non-randomized | refractory/relapsed non-Hodgkin lymphoma | safety and tolerability |
NCT02953782 | I/II | Anti-CD47 antibody (Hu5F9-G4) in combination with cetuximab | single-arm, non-randomized | solid tumors and CRC | safety and tolerability |
Tumor Antigens | Proteins | Specificity | Advantages | Disadvantages |
---|---|---|---|---|
Differentiation antigens | MART1, GP100, PAP, CEA | Low | high prevalence, cheap off-the-shelf products, allow conjugation | high probability of nonspecificity and side effects |
Overexpressed antigens | WT1, MUC1, ERBB2 | Low | high prevalence, cheap off-the-shelf products, allow conjugation | high probability of nonspecificity and side effects |
Viral antigens | HPV-, EBV-derived proteins | High | very specific, allow conjugation | limited prevalence of virus-associated tumors |
Cancer-Germline antigens | NY-ESO-1, MAGE, GAGE, BAGE | High | specific, cheap off-the-shelf products allow conjugation | not exclusive to cancer |
Mutated neoantigens | mutated tumor neoantigens | Highest | very specific, allow conjugation | expensive, labor- and technology intensive |
Whole tumor antigens | lysate of cancer material | Variable | no need for neoantigen identification, contain additional DC-activating factors | limited cancer material, uncontrolled material |
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Kunimasa, K.; Goto, T. Immunosurveillance and Immunoediting of Lung Cancer: Current Perspectives and Challenges. Int. J. Mol. Sci. 2020, 21, 597. https://doi.org/10.3390/ijms21020597
Kunimasa K, Goto T. Immunosurveillance and Immunoediting of Lung Cancer: Current Perspectives and Challenges. International Journal of Molecular Sciences. 2020; 21(2):597. https://doi.org/10.3390/ijms21020597
Chicago/Turabian StyleKunimasa, Kei, and Taichiro Goto. 2020. "Immunosurveillance and Immunoediting of Lung Cancer: Current Perspectives and Challenges" International Journal of Molecular Sciences 21, no. 2: 597. https://doi.org/10.3390/ijms21020597
APA StyleKunimasa, K., & Goto, T. (2020). Immunosurveillance and Immunoediting of Lung Cancer: Current Perspectives and Challenges. International Journal of Molecular Sciences, 21(2), 597. https://doi.org/10.3390/ijms21020597