Abstract
Immune checkpoint inhibitors (ICIs) targeting the programed cell-death protein 1 (PD-1) or its ligand PD-L1 and cytotoxic T-lymphocyte antigen 4 (CTLA-4) pathways have improved the survival for patients with solid tumors. Unfortunately, durable clinical responses are seen in only 10–40% of patients at the cost of potential immune-related adverse events. In the tumor microenvironment (TME), tumor cells can influence the microenvironment by releasing extracellular signals and generating peripheral immune tolerance, while the immune cells can affect the initiation, growth, proliferation, and evolution of cancer cells. Currently, translational biomarkers that predict responses to ICIs include high PD-L1 tumor proportion score, defective DNA mismatch repair, high microsatellite instability, and possibly high tumor mutational burden. Characterization of immune cells in the TME, such as tumor-infiltrating lymphocytes, T-cell gene expression profile, T-cell receptor sequencing, and peripheral blood biomarkers are being explored as promising biomarkers. Recent neoadjuvant studies have integrated the real-time assessment of both molecular and immune biomarkers using the tissue and blood specimens simultaneously and longitudinally. This review summarizes the current knowledge and progress in developing translational biomarkers and rational combinational strategies to improve the efficacy of ICIs tailored to individual cancer patients.
Keywords
- Immune checkpoint inhibitors (ICIs)
- Programed cell-death protein 1 (PD-1)
- Programed cell-death protein ligand 1 (PD-L1)
- Cytotoxic T-lymphocyte antigen 4 (CTLA-4)
- Translational biomarker
- Tumor microenvironment (TME)
- Tumor mutational burden (TMB)
- Gene expression profile (GEP)
- Tumor-infiltrating lymphocytes (TILs)
- Blood biomarkers
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- ADCC:
-
Antibody-dependent cell-mediated cytotoxicity
- ALC:
-
Absolute lymphocyte counts
- ANC:
-
Absolute neutrophil counts
- APCs:
-
Antigen-presenting cells
- B2M:
-
Beta-2-microglobulin
- BRCA:
-
Breast cancer
- bTMB:
-
Blood tumor mutation burden
- CAMLs:
-
Cancer-associated macrophage-like cells
- CCR:
-
C-C Motif Chemokine Receptor
- CE:
-
Conformité Européene
- CRP:
-
C-reaction protein
- CTL:
-
Cytotoxic T lymphocytes
- CTLA-4:
-
Cytotoxic T-lymphocyte antigen 4
- CTCs:
-
Circulating tumor cells
- CXCR:
-
C-X-C Motif Chemokine Receptor
- dMMR:
-
Deficient mismatch repair
- dNLR:
-
Derived neutrophil-to-lymphocyte ratio
- ECM:
-
Extracellular matrix
- ELISPOT:
-
Enzyme-linked immune absorbent spot
- FFPE:
-
Formalin-fixed paraffin-embedded
- FOXP3:
-
Forkhead box P3
- GEP:
-
Gene expression profile
- HLA:
-
Human leukocyte antigen
- HNSCC:
-
Head and neck squamous cell carcinomas
- ICIs:
-
Immune checkpoint inhibitors
- ICOS:
-
Inducible costimulator
- IDO:
-
Indoleamine-pyrrole 2,3-dioxygenase
- IFN-γ:
-
Interferon-gamma
- IFNGR1:
-
IFN-γ receptor 1
- IFNGR2:
-
IFN-γ receptor 2
- IRF1:
-
IFN regulatory factor 1
- IHC:
-
Immunohistochemical stain
- irAEs:
-
Immune-related adverse events
- IL:
-
Interleukin,
- JAK:
-
Janus kinase
- LAG3:
-
Lymphocyte-activation protein 3
- LDH:
-
Lactate dehydrogenase
- LIPI:
-
Lung immune prognostic index
- NGS:
-
Next-generation sequencing
- NSCLC:
-
Non-small cell lung cancer
- mAbs:
-
Monoclonal antibodies
- MDSC:
-
Myeloid-derived suppressor cell
- MHC:
-
Major histocompatibility complex
- MSI-H:
-
Microsatellite instability–high
- NK:
-
Natural killer
- OS:
-
Overall survival
- PBMC:
-
Peripheral blood mononuclear cell
- pCR:
-
Pathological complete response
- PD-1:
-
Programed cell-death protein 1
- PD-L1:
-
Programed cell-death protein ligand 1
- PDX:
-
Patient-derived xenograft
- PFS:
-
Progression-free survival
- STAT:
-
Signal transducer and activator of transcription
- STING:
-
Stimulator of interferon gene
- TAAs:
-
Tumor-associated antigens
- TCR:
-
T cell receptor
- TGF-β:
-
Transforming growth factor-beta
- TILs:
-
Tumor-infiltrating lymphocytes
- TIGIT:
-
T cell immunoreceptor with Ig and ITIM domains
- TIM3:
-
T cell immunoglobulin and mucin domain-3
- TMB:
-
Tumor mutational burden
- TME:
-
Tumor microenvironment
- TPS:
-
Total proportion score
- WES:
-
Whole exome sequencing
- VEGF:
-
Vascular endothelial growth factor
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Chen, J.A., Ma, W., Yuan, J., Li, T. (2020). Translational Biomarkers and Rationale Strategies to Overcome Resistance to Immune Checkpoint Inhibitors in Solid Tumors. In: Lee, P., Marincola, F. (eds) Tumor Microenvironment. Cancer Treatment and Research, vol 180. Springer, Cham. https://doi.org/10.1007/978-3-030-38862-1_9
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