Recent Advancements in the Mechanisms Underlying Resistance to PD-1/PD-L1 Blockade Immunotherapy
Abstract
:Simple Summary
Abstract
1. Introduction
2. The Expression of PD-L1 Levels Predicting Resistance and Poor Prognosis
3. PD-L1-Induced Resistance
3.1. PD-L1-Mediated Immune Resistance
3.2. Signaling Pathways and Factors Involved in PD-L1-Induced Resistance
4. Key Mechanisms Underlying Resistance to PD-1/PD-L1 Blockade
4.1. Aberrant PD-L1 Expression
4.2. Paucity of PD-L1 Expression
4.3. Aberrant Antigen Expression, Presentation and Recognition
4.4. Aberrant Immunity of T-Cells
4.4.1. Insufficient T Lymphocytes Infiltration
4.4.2. Dysfunction of T-Cells
4.4.3. Exhausted T-Cells
5. Tumor-Suppressing Microenvironment
5.1. Tregs
5.2. MDSCs
5.3. TAMs
5.4. IDO
5.5. VEGFA
5.6. Immunosuppressive Cytokines
6. Activation of Alternative Immune Checkpoints
6.1. TIM-3
6.2. HHLA2
6.3. VISTA
6.4. LAG-3
6.5. CTLA-4
6.6. Siglec-15
6.7. TIGHT
6.8. BTLA
7. Current Combination Therapies with PD-1/PD-L1 Inhibitors
8. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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Yuan, Y.; Adam, A.; Zhao, C.; Chen, H. Recent Advancements in the Mechanisms Underlying Resistance to PD-1/PD-L1 Blockade Immunotherapy. Cancers 2021, 13, 663. https://doi.org/10.3390/cancers13040663
Yuan Y, Adam A, Zhao C, Chen H. Recent Advancements in the Mechanisms Underlying Resistance to PD-1/PD-L1 Blockade Immunotherapy. Cancers. 2021; 13(4):663. https://doi.org/10.3390/cancers13040663
Chicago/Turabian StyleYuan, Yu, Abdalla Adam, Chen Zhao, and Honglei Chen. 2021. "Recent Advancements in the Mechanisms Underlying Resistance to PD-1/PD-L1 Blockade Immunotherapy" Cancers 13, no. 4: 663. https://doi.org/10.3390/cancers13040663