Immune escape to PD-L1/PD-1 blockade: seven steps to success (or failure)
Open accessAbstract
The emergence of programmed death-ligand 1 (PD-L1)/programmed death-1 (PD-1)-targeted therapy has demonstrated the importance of the PD-L1 : PD-1 interaction in inhibiting anticancer T-cell immunity in multiple human cancers, generating durable responses and extended overall survival. However, not all patients treated with PD-L1/PD-1-targeted therapy experience tumor shrinkage, durable responses, or prolonged survival. To extend such benefits to more cancer patients, it is necessary to understand why some patients experience primary or secondary immune escape, in which the immune response is incapable of eradicating all cancer cells. Understanding immune escape from PD-L1/PD-1-targeted therapy will be important to the development of rational immune-combination therapy and predictive diagnostics and to the identification of novel immune targets. Factors that likely relate to immune escape include the lack of strong cancer antigens or epitopes recognized by T cells, minimal activation of cancer-specific T cells, poor infiltration of T cells into tumors, downregulation of the major histocompatibility complex on cancer cells, and immunosuppressive factors and cells in the tumor microenvironment. Precisely identifying and understanding these mechanisms of immune escape in individual cancer patients will allow for personalized cancer immunotherapy, in which monotherapy and combination immunotherapy are chosen based on the presence of specific immune biology. This approach may enable treatment with immunotherapy without inducing immune escape, resulting in a larger proportion of patients obtaining clinical benefit.
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Most patients could not benefit from α-PD-1/PD-L1 treatments, owing to primary or acquired treatment resistance.
“Although α-PD-1/PD-L1 therapies exhibit potent antitumor effects in some patients, most patients could not benefit from α-PD-1/PD-L1 treatments, owing to primary or acquired treatment resistance [13].”
From Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022) · cites this paper as [13]
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- Authors
- Kim, J. M., & Chen, D. S.
- Affiliations
- Genentech (US)
- Corresponding author
- Chen, D.S.
- ORCID
- Chen, D.S.
- Venue
- Annals of Oncology
- Publisher
- Elsevier BV
- Published
- 2016-08
- Volume
- 27
- Issue
- 8
- Pages
- 1492-1504
- ISSN
- 0923-7534 (ISSN-L)
- OpenAlex
- W2402433991
- Cited by
- 648
- References
- 187
- Citations by year
- 2026: 22 · 2025: 61 · 2024: 72 · 2023: 87 · 2022: 127 · 2021: 81 · 2020: 66 · 2019: 53 · 2018: 41 · 2017: 35 · 2016: 3
- FWCI
- 4.38
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Annals of Oncology (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- immune evasion, immune checkpoint inhibitors, cancer immunotherapy, tumor-specific T cells, T cell infiltration, MHC downregulation, tumor microenvironment, immunosuppressive cells, tumor antigens, predictive biomarkers, combination immunotherapy, personalized cancer immunotherapy
- MeSH terms
- Antibodies, Monoclonal, Humans, Immunotherapy, Neoplasms, T-Lymphocytes, Molecular Targeted Therapy, Tumor Microenvironment, B7-H1 Antigen, Programmed Cell Death 1 Receptor
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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