Primary and Acquired Resistance to Immunotherapy in Lung Cancer: Unveiling the Mechanisms Underlying of Immune Checkpoint Blockade Therapy
Abstract
:Simple Summary
Abstract
1. Introduction
2. Clinical Management of Patients with Lung Cancer
3. Immunotherapy for Lung Cancer
3.1. Nonspecific Immunotherapies
3.2. Oncolytic Viruses (OVs)
3.3. Adoptive T-Cell Immunotherapy
3.4. Cancer Vaccines
3.5. Monoclonal Antibodies (mAbs)
4. Impact of Immunotherapy on the Survival of Patients with Lung Cancer
5. Resistance to Immune Checkpoints in Lung Cancer Immunotherapy
5.1. Tumor Neoantigen Burden
5.2. Effector T-Cell Infiltration in the TME
5.3. Epigenetic Modulation
5.4. The Innate Anti-PD-1 Resistance (IPRES) Gene Signature
5.5. PD-L1 Expression
5.6. T-Cell Exhaustion
5.7. Genomic Drivers
5.8. Enteric Microbiome
6. Potential Biomarkers of Resistance to Immunotherapy in Lung Cancer
7. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
ADC | Adenocarcinoma |
ADCC | Antibody-dependent cell-mediated cytotoxicity |
AdMA3 | Adenovirus/MAGE-A3 virus |
ALK | Anaplastic lymphoma kinase |
BRAF | v-Raf murine sarcoma viral oncogene homolog B |
CAR | Chimeric antigen receptor |
CDC | Complement-dependent cytotoxicity |
CI | Confidence interval |
CIK | Cytokine-induced killer cell |
CT | Chemotherapy |
ctDNA | Circulating tumor DNA |
CTL | Cytotoxic T lymphocyte |
CTLA-4 | Cytotoxic T lymphocyte-associated antigen 4 |
CVA21 | Coxsackievirus A21 |
CV-B3 | Coxsackievirus type B3 |
DC | Dendritic cell |
DCR | Disease control rates |
dMMR | DNA mismatch repair deficiency |
dsDNA | Double-stranded DNA |
EGF | Epidermal growth factor |
EGFR | Epidermal growth factor receptor |
EML4 | Echinoderm microtubule associated protein-like 4 |
ETC | Endogenous peripheral blood-derived T-cells |
EV | Extracellular vesicle |
FASL | FAS antigen ligand |
FDA | Food and Drug Administration |
FGFR1 | Fibroblast growth factor receptor 1 |
GM-CSF | Granulocyte Macrophage colony-stimulating factor |
GzmB | Granzyme B |
HER2 | Human epidermal growth factor receptor 2 |
HR | Hazard ratio |
HSV-1 | Herpes simplex virus type 1 |
ICI | Immune checkpoints inhibitor |
IDO1 | Indoleamine 2,3-dioxygenases |
IFN-γ | Interferon-γ |
IL-2 | Interleukin-2 |
IT | Immunotherapy |
iTreg | Inducible regulatory T cell |
LCC | Large cell carcinoma |
LOH | Loss of heterozygosity |
mAb | Monoclonal antibody |
MDSC | Myeloid-derived suppressor cell |
MET | Hepatocyte growth factor receptor |
MG1MA3 | MG1 Maraba/MAGE-A3 virus |
MSI-H | Microsatellite instability-high |
MV | Measles virus |
MYXV | Myxoma virus |
NSCLC | Non-small cell lung cancer |
ORR | Objetive response rate |
OS | Overall survival |
OV | Oncolytic virus |
PBMCs | Peripheral blood mononuclear cells |
PD-1 | Programmed cell death protein 1 |
PD-L1 | Programmed cell death ligand 1 |
PFS | Progression-free survival |
PI3K | Phosphoinositol 3-kinase |
ROS1 | Receptor tyrosine kinase ROS proto-oncogene 1 |
RT | Radiotherapy |
RTK | Tyrosine kinase receptor |
SCC | Squamous cell carcinoma |
SCLC | Small cell lung cancer |
sPD-L1 | soluble forms of PD-L1 |
SUPRA CAR | Split, universal, and programmable chimeric antigen receptor system |
TAA | Tumor-associated antigen |
TAM | Tumor-associated macrophage |
TCR | T-cell receptor |
TCR-T | TCR-engineered T-cells |
TIL | tumor-infiltrating lymphocyte |
TKI | Tyrosine kinase receptor inhibitor |
TMB | Tumor mutation burden |
TME | Tumor microenvironment |
TNF-α | Tumor necrosis factor-α |
Treg | Regulatory T cell |
VEGF | Vascular endothelial growth factor |
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Antigen Target | Monoclonal Antibody Name | Clinical Trial ID (https://clinicaltrials.gov) |
---|---|---|
B7-H3 | Enoblituzumab (MGA271) | NCT02475213 |
BTLA | TAB004 | NCT04137900 |
CD137 | BMS-663513 | NCT00461110 |
CD40 | APX005M | NCT02482168 |
SEA-CD40 | NCT02376699 | |
CD44 v6 | Bivatuzumab | NCT02204059 |
CD73 | CPI-006 | NCT03454451 |
Oleclumab | NCT04262388 | |
CEA | Yttrium Y 90 anti-CEA monoclonal antibody cT84.66 | NCT00738452 |
Yttrium Y 90 anti-CEA monoclonal antibody MN-14 (90Y-hMN-14), indium In 111 anti-CEA monoclonal antibody MN-14 | NCT00006458 | |
CEACAM1 | CM-24 | NCT02346955 |
c-MET | Sym015 | NCT02648724 |
CSF1R | Cabiralizumab | NCT03502330 |
CTLA-4 | Ipilimumab * | NCT03001882, NCT02350764 |
ONC-392 | NCT04140526 | |
REGN4659 | NCT03580694 | |
Tremelimumab | NCT02542293, NCT02000947 | |
DLL3 | Rovalpituzumab tesirine | NCT03000257 |
DLL4 | Demcizumab | NCT01189968 |
EpCAM | Tucotuzumab celmoleukin | NCT00016237 |
ErbB1/EGFR | Cetuximab | NCT00986674 |
Futuximab/modotuximab (Sym004) | NCT02924233 | |
Necitumumab * | NCT02496663 | |
Nimotuzumab | NCT01393080 | |
Matuzumab | NCT00111839 | |
Panitumumab (ABX-EGF) | NCT00034346 | |
Pertuzumab | NCT03845270 | |
SCT200 | NCT03808701 | |
ErbB2/HER2 | Trastuzumab (Herceptin) | NCT04285671, NCT03505710, NCT03845270 |
ErbB3/HER3 | Seribantumab (MM-121) | NCT02387216, NCT00994123 |
GDF15 | NGM120 | NCT04068896 |
GM2 Ganglioside | BIW-8962 | NCT01898156 |
HGF | Ficlatuzumab (AV-299) | NCT01039948 |
ICOS | GSK3359609 | NCT03693612 |
KY1044 | NCT03829501 | |
Vopratelimab | NCT03989362 | |
IGF-1, IGF-2 | Xentuzumab | NCT02191891 |
IGF-1R | Cixutumumab | NCT00778167, NCT00986674 |
Dalotuzumab | NCT00951444 | |
Figitumumab (CP-751,871) | NCT00560573 | |
Ganitumab (AMG 479) | NCT00807612 | |
IL1RAP | Nidanilimab (CAN 04) | NCT03267316 |
LAG-3 | TSR-033 | NCT02817633 |
LIF | MSC-1 | NCT03490669 |
Mesothelin | Amatuximab | NCT00325494 |
Anetumab Ravtansine | NCT03455556 | |
LMB-100 | NCT04027946 | |
CD134 | INCAGN01949 | NCT02923349 |
PD-1 | BCD-100 | NCT03288870 |
Budigalimab (ABBV-181) | NCT03000257 | |
Camrelizumab (SHR-1210) | NCT03527251 | |
Cemiplimab | NCT03580694 | |
Dostarlimab | NCT02715284 | |
Nivolumab * | NCT04043195, NCT04023617 | |
Pembrolizumab * | NCT04393883, NCT03053856 | |
Retifanlimab (MGA012) | NCT02475213 | |
Sasanlimab (PF-06801591) | NCT04181788 | |
SCT-I10A | NCT04171284 | |
Serplulimab (HLX10) | NCT04033354 | |
Sintilimab | NCT03812549 | |
Spartalizumab | NCT04323436, NCT04000529 | |
Tislelizumab | NCT03358875 | |
Toripalimab | NCT04158440, NCT04304248 | |
Zimberelimab (AB122) | NCT04262856, NCT03629756 | |
PDGF-R α | Olaratumab | NCT00918203 |
PD-L1 | Adebrelimab (SHR-1316) | NCT04316364 |
Atezolizumab * | NCT03977467, NCT03645330 | |
Avelumab | NCT03158883 | |
Cosibelimab | NCT03212404 | |
Durvalumab * | NCT02000947, NCT03694236 | |
Sugemalimab (CS1001) | NCT03789604 | |
TQB2450 | NCT03910127 | |
Phosphatidylserine (Ptd-L-Ser or PS) | Bavituximab | NCT01160601, NCT01138163 |
PSMA | 177Lu-J591 | NCT00967577 |
RAAG12 | RAV12 | NCT00101972 |
sCLU | AB-16B5 | NCT04364620 |
SEMA4D | Pepinemab | NCT03268057 |
TF | MORAb-066 | NCT01761240 |
TGFB | Fresolimumab | NCT02581787 |
TIM-3 | Cobolimab (TSR-022) | NCT02817633 |
INCAGN02390 | NCT00994123 | |
MBG453 | NCT02608268 | |
TRAIL-R1 | TRM-1 (HGS-ETR1) | NCT00092924 |
TRAIL-R2 | Conatumumab (AMG 655) | NCT00534027 |
VEGF | Bevacizumab * | NCT03836066, NCT03779191 |
GB222 | NCT04175158 | |
LY01008 | NCT03533127 | |
QL1101 | NCT03195569 | |
VEGFR2 | Alacizumab pegol (CDP791) | NCT00152477 |
Ramucirumab (IMC-1121B) * | NCT01160744 | |
α5β1 integrin | Volociximab | NCT00666692 |
Antigen Target | Monoclonal Antibody Name | Clinical Trial ID (https://clinicaltrials.gov) |
---|---|---|
BEC-2 | Mitumomab | NCT00037713 |
CD56 | Lorvotuzumab mertansine | NCT00346385 |
CEA | Yttrium Y 90 anti-CEA monoclonal antibody MN-14 (90Y-hMN-14), indium In 111 anti-CEA monoclonal antibody MN-14 | NCT00006347 |
CTLA-4 | Ipilimumab | NCT03575793 |
Tremelimumab | NCT02701400 | |
DLL3 | 89Zr-DFO-SC16.56 | NCT04199741 |
Rovalpituzumab Tesirine | NCT03000257 | |
EpCAM | Tucotuzumab celmoleukin | NCT00016237 |
ErbB1/EGFR | Cetuximab | NCT00104910 |
ErbB2/HER2 | Trastuzumab (Herceptin) | NCT00028535 |
GD2 ganglioside | Dinutuximab | NCT03098030 |
MOAB 3F8 | NCT00003022 | |
GD3 ganglioside | Mitumomab | NCT00006352 |
GM2 Ganglioside | BIW-8962 | NCT01898156 |
IGF-1R | Cixutumumab | NCT00887159 |
Dalotuzumab | NCT00869752 | |
Lewis-Y | Hu3S193 | NCT00084799 |
PD-1 | Budigalimab (ABBV-181) | NCT03000257 |
Camrelizumab (SHR1210) | NCT03755115, NCT03417895 | |
Nivolumab * | NCT03382561 | |
Pembrolizumab | NCT03319940 | |
Serplulimab (HLX10) | NCT04063163 | |
PD-L1 | Atezolizumab * | NCT03262454 |
Durvalumab * | NCT02701400 | |
TQB2450 | NCT04234607 | |
ZKAB001 | NCT04346914 | |
TAA | Bevacizumab | NCT00079040 |
TIM-3 | INCAGN02390 | NCT03652077 |
VEGF | SC-002 | NCT02500914 |
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Boyero, L.; Sánchez-Gastaldo, A.; Alonso, M.; Noguera-Uclés, J.F.; Molina-Pinelo, S.; Bernabé-Caro, R. Primary and Acquired Resistance to Immunotherapy in Lung Cancer: Unveiling the Mechanisms Underlying of Immune Checkpoint Blockade Therapy. Cancers 2020, 12, 3729. https://doi.org/10.3390/cancers12123729
Boyero L, Sánchez-Gastaldo A, Alonso M, Noguera-Uclés JF, Molina-Pinelo S, Bernabé-Caro R. Primary and Acquired Resistance to Immunotherapy in Lung Cancer: Unveiling the Mechanisms Underlying of Immune Checkpoint Blockade Therapy. Cancers. 2020; 12(12):3729. https://doi.org/10.3390/cancers12123729
Chicago/Turabian StyleBoyero, Laura, Amparo Sánchez-Gastaldo, Miriam Alonso, José Francisco Noguera-Uclés, Sonia Molina-Pinelo, and Reyes Bernabé-Caro. 2020. "Primary and Acquired Resistance to Immunotherapy in Lung Cancer: Unveiling the Mechanisms Underlying of Immune Checkpoint Blockade Therapy" Cancers 12, no. 12: 3729. https://doi.org/10.3390/cancers12123729