Acquired Resistance to Immune Checkpoint Blockade Therapies
Abstract
:1. Introduction
2. Mechanisms of Acquired ICBT Resistance
2.1. Loss of Tumor Cell Visibility to Immune Cells
2.2. Loss of Tumor Cells Sensitivity to Immune Effectors
2.3. Compensation of Alternative Immune Checkpoints on T Cells
2.4. Tumor Cell-Mediated T-Cell Suppression
2.5. Tumor Pathologic Transformation and Epithelial–Mesenchymal Transition
3. Detection of Acquired ICBT Resistance
4. Principles for Overcoming Acquired ICBT Resistance
5. Conclusions and Future Directions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Approaches | Mechanisms of Approach | Relevance to Anti-Tumor Immune Mechanisms | Reference |
---|---|---|---|
Radiographic imaging | Direct measurement of tumor burden | No | [55] |
Molecular imaging | Measurement of immune protein expression on whole tumor tissues | Yes | [65,66] |
Serum tumor biomarkers | Estimation of tumor burden by quantifying serum tumor antigens or genetic material | Marker-dependent | [67,68] |
Circulating tumor cells | Estimation of tumor burden by quantifying and featuring circulating tumor cells | Marker-dependent | [69] |
PD-L1 expression | Assessment of the proportion of PD-L1-positive tumor cells, immune cells, or both on tumor tissue sections | Yes | [70,71] |
Tumor-infiltrating lymphocyte | Assessment of T cells at invasive tumor margin or tumor parenchyma | Yes | [72,73] |
T-cell receptor sequencing | Assessment of T-cell clonality by sequencing of T-cell receptor β-chain | Yes | [74] |
Mutational and neoantigen burden | Exome sequencing to assess non-synonymous somatic mutations with antigenic prediction | Yes | [15] |
DNA mismatch repair genes status | Assessment of mismatch repair genes status in tumor parenchyma | Yes | [75] |
Immune gene signatures | Assessment of immune gene expression signature from the tumor microenvironment | Yes | [76] |
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Zhao, X.; Wangmo, D.; Robertson, M.; Subramanian, S. Acquired Resistance to Immune Checkpoint Blockade Therapies. Cancers 2020, 12, 1161. https://doi.org/10.3390/cancers12051161
Zhao X, Wangmo D, Robertson M, Subramanian S. Acquired Resistance to Immune Checkpoint Blockade Therapies. Cancers. 2020; 12(5):1161. https://doi.org/10.3390/cancers12051161
Chicago/Turabian StyleZhao, Xianda, Dechen Wangmo, Matthew Robertson, and Subbaya Subramanian. 2020. "Acquired Resistance to Immune Checkpoint Blockade Therapies" Cancers 12, no. 5: 1161. https://doi.org/10.3390/cancers12051161