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Turning cold tumors hot: from molecular mechanisms to clinical applications
Abstract
Immune checkpoint blockade (ICB) therapies have achieved clinical benefit, but most 'immune-cold' solid tumors are not responsive. The diversity of immune evasion mechanisms remains a key obstacle in turning nonresponsive 'cold' tumors into responsive 'hot' ones. Therefore, exploring the mechanisms of such transitions and tumor immunotyping can provide significant insights into designing effective therapeutic strategies against cancer. Here, we focus on the latest advances regarding local and systemic regulatory mechanisms of immune responses in cold and hot tumors. We also highlight the necessity for tumor immunotyping through the assessment of multiple immunological variables using various diagnostic techniques and biomarkers. Finally, we discuss the challenges and potential clinical applications of immunophenotyping to turn cold tumors hot, which may further guide combined immunotherapies.
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“As noted above, based on their TME, tumors can be categorized into two general types: ‘hot’ tumors, distinguished by an immunosupportive TME and a positive response to immunotherapy, and ‘cold’ or non-immune reactive tumors exhibiting a poor response to immunotherapy and characterized by an immunosuppressive TME (Zhang et al., 2022; Benoit et al., 2023).”
From Microphysiological systems as models for immunologically ‘cold’ tumors (2024) · cites this paper as Zhang et al., 2022
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Stanniocalcin 1 is a phagocytosis checkpoint driving tumor immune resistance
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Sex Hormones and Anticancer Immunity
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Turning tumors from cold to inflamed to improve immunotherapy response
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Cold and hot tumors: from molecular mechanisms to targeted therapy
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CD8 T-cell subsets: heterogeneity, functions, and therapeutic potential
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“These “ hot ” tumors exhibit a more favorable response to immunotherapies than “ cold ” tumors, which lack Tc1 cell in fi ltration 28,29 .”
BackgroundTertiary lymphoid structures in anticancer immunity
Teillaud, J., Houel, A., Panouillot, M., Riffard, C., & Dieu‐Nosjean, M. (2024) · Nature reviews. Cancer · doi:10.1038/s41568-024-00728-0 · Cited by 322
“Finally, it is unclear whether ‘cold’ tumours that do not exhibit substantial immune cell infiltrates could be made ‘hot’ when using inducers of TLS 189 .”
Tumour circular RNAs elicit anti-tumour immunity by encoding cryptic peptides
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Metadata
- Authors
- Zhang, J., Huang, D., Saw, P. E., & Song, E.
- Affiliations
- Sun Yat-sen University (CN)
- Corresponding author
- Saw, Phei Er
- Song, Erwei
- Venue
- Trends in Immunology
- Publisher
- Elsevier BV
- Published
- 2022-07
- Volume
- 43
- Issue
- 7
- Pages
- 523-545
- ISSN
- 1471-4906 (ISSN-L)
- OpenAlex
- W4281490788
- Cited by
- 534
- References
- 189
- Citations by year
- 2026: 72 · 2025: 145 · 2024: 162 · 2023: 133 · 2022: 22
- FWCI
- 14.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Trends in Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81621004, 81720108029, 81930081, 91940305, 92159303)
- Guangdong Science and Technology Department (2020B1212030004, 2020B1212060018)
- Guangzhou Municipal Science and Technology Bureau (20212200003)
- 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
- cold tumors, immune evasion, immune checkpoint blockade, tumor microenvironment, immune regulation, biomarkers, combination immunotherapy, solid tumors
- MeSH terms
- Humans, Immunity, Immunotherapy, Neoplasms, Tumor Microenvironment
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