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The efficacy of PD-1/PD-L1 blockade in cold cancers and future perspectives
Abstract
Colorectal cancer (CRC), and breast, ovarian, pancreatic and prostate cancers are generally considered as low immune-reactive cancers that represent either limited infiltration of immune cells or extensive infiltration of immunosuppressive T cells. Interaction between programmed death ligand 1 (PD-L1) with programmed death-1 receptor (PD-1) is important for immune evasion. Tumors positive for PD-L1 generally show higher responses to the immune checkpoint inhibition (ICI); however, the high presence of PD-L1 in a tumor is a predictor of poor prognosis. Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, but responses to the ICI is meaningful. It seems that in a tumor both the PD-L1 expression and TIL infiltration is required for improving responses to the anti-PD-1/PD-L1 immunotherapy. Combination of anti-PD-1/PD-L1 with immune modulatory drugs, such as C-X-C chemokine receptor type 4 (CXCR4), poly (ADP-ribose) polymerase (PARP) or transforming growth factor (TGF)-β inhibitors has shown meaningful clinical benefits.
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“However, the challenge persists in treating ‘cold’ tumors with ICIs (Majidpoor and Mortezaee, 2021).”
From Microphysiological systems as models for immunologically ‘cold’ tumors (2024) · cites this paper as Majidpoor and Mortezaee, 2021
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Programmed death ligand 1 (PD-L1) plays a vital part in DC tolerogenicity induced by IFN-γ
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Metadata
- Authors
- Majidpoor, J., & Mortezaee, K.
- Affiliations
- Gonabad University of Medical Sciences (IR)
- Kurdistan University of Medical Sciences (IR)
- Corresponding author
- Mortezaee, Keywan
- Venue
- Clinical Immunology
- Publisher
- Elsevier BV
- Published
- 2021-05
- Volume
- 226
- Pages
- 108707
- ISSN
- 1521-6616 (ISSN-L)
- OpenAlex
- W3134731856
- Cited by
- 236
- References
- 123
- Citations by year
- 2026: 11 · 2025: 24 · 2024: 77 · 2023: 60 · 2022: 42 · 2021: 22
- FWCI
- 6.36
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Clinical Immunology (publishedVersion)
- PubMed (publishedVersion)
- 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
- PD-1/PD-L1 blockade, immune checkpoint inhibitors, cold tumors, immune evasion, triple-negative breast cancer, colorectal cancer, tumor-infiltrating lymphocytes, PD-L1 expression, CXCR4, PARP inhibitors, TGF-β inhibitors, combination immunotherapy
- MeSH terms
- Immune Checkpoint Inhibitors, Humans, Immunologic Factors, Immunotherapy, Neoplasms, T-Lymphocytes, Lymphocytes, Tumor-Infiltrating, B7-H1 Antigen, Programmed Cell Death 1 Receptor
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