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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The challenge persists in treating 'cold' tumors with immune checkpoint inhibitors (ICIs).
“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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- 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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