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The importance of immune checkpoints in immune monitoring: A future paradigm shift in the treatment of cancer
Open accessAbstract
The growth and development of cancer are directly correlated to the suppression of the immune system. A major breakthrough in cancer immunotherapy depends on various mechanisms to detect immunosuppressive factors that inhibit anti-tumor immune responses. Immune checkpoints are expressed on many immune cells such as T-cells, regulatory B cells (Bregs), dendritic cells (DCs), natural killer cells (NKs), regulatory T (Tregs), M2-type macrophages, and myeloid-derived suppressor cells (MDSCs). Immune inhibitory molecules, including CTLA-4, TIM-3, TIGIT, PD-1, and LAG-3, normally inhibit immune responses via negatively regulating immune cell signaling pathways to prevent immune injury. However, the up-regulation of inhibitory immune checkpoints during tumor progression on immune cells suppresses anti-tumor immune responses and promotes immune escape in cancer. It has recently been indicated that cancer cells can up-regulate various pathways of the immune checkpoints. Therefore, targeting immune inhibitory molecules through antibodies or miRNAs is a promising therapeutic strategy and shows favorable results. Immune checkpoint inhibitors (ICIs) are introduced as a new immunotherapy strategy that enhance immune cell-induced antitumor responses in many patients. In this review, we highlighted the function of each immune checkpoint on different immune cells and therapeutic strategies aimed at using monoclonal antibodies and miRNAs against inhibitory receptors. We also discussed current challenges and future strategies for maximizing these FDA-approved immunosuppressants' effectiveness and clinical success in cancer treatment.
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“Nonetheless, it has been proved that this phenotype also has increased immunogenic properties inducing high immune cell infiltration, particularly from tumor-infiltrating lymphocytes [12,43].”
From Current and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy (2024) · cites this paper as [43]
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BackgroundTargeting “don’t eat me” signal: breast cancer immunotherapy
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“In recent years, immunotherapy has become an important therapeutic method for multiple tumor types (Alemohammad et al., 2021; Cai et al., 2021); thus, a possible correlation between the risk score and immune infiltration was assessed.”
MethodZhou, Q., Lan, L., Wang, W., Xu, X., & Wang, W. (2023) · Aging · doi:10.18632/aging.205247 · Cited by 3
Immune Checkpoint Inhibitors in Cancer Immunotherapy
Hussain, F. H. N., & Raza, A. (2024) · Advances in medical diagnosis, treatment, and care (AMDTC) book series · doi:10.4018/979-8-3693-3976-3.ch004 · Cited by 3
Koh, C. C., Gollob, K. J., & Dutra, W. O. (2025) · Pathogens · doi:10.3390/pathogens14020188 · Cited by 2
“These endogenous small RNAs, called miRNAs, bind complexly to complementary mRNAs to influence mRNA degradation or disrupt protein translation [63–65].”
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Immune escape mechanisms and therapeutic advances in virus-associated hematological malignancies
Li, T., Wang, C., Xiao, Q., Zhang, X., Zailin, Y., Li, J., & Liu, Y. (2026) · Blood Cancer Journal · doi:10.1038/s41408-026-01453-7 · Cited by 2
“Research shows that high TIM-3 expression is closely associated with tumor immune escape, and inhibiting TIM-3 can restore T-cell function and enhance anti-tumor immune responses [78].”
Chen, Y. N., 罗晓丁, Wang, Z., Duan, J., & Xiao, P. (2026) · Pharmacological Research · doi:10.1016/j.phrs.2026.108256 · Cited by 1
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Wu, Y., Yao, Z., Zhang, J., Han, C., Kang, K., & Zhao, A. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1058819 · Cited by 1
Identification of a lipid metabolism-related gene for cancer immunotherapy
Jiang, X., Du, W., Shi, C., Kang, M., Song, Q., Zhang, L., & Pei, D. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1186064 · Cited by 1
“It is well established that immune escape and immune infiltration are associated with tumor growth and development (Alemohammad et al., 2022).”
BackgroundImmuno-Oncology In Cancer Cervix Treatments: Literature Review
Naser, M., Nasr, M., & Shehata, L. H. (2023) · International Journal of Progressive Sciences and Technologies · doi:10.52155/ijpsat.v41.1.5708 · Cited by 1
The enigma of LAG3 receptor in hematological malignancies
Kreiniz, N., Polliack, A., & Tadmor, T. (2022) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.1080/10428194.2022.2133543 · Cited by 1
Belastung, Muskelreparatur, Muskelremodulation, Immunsystem
Laube, W. (2023) · Springer eBooks · doi:10.1007/978-3-662-67753-7_11
P3H1 as a novel prognostic biomarker correlates with immune infiltratePreprint
Wu, C.-M., You, X., Li, B., Wang, Q., Li, M., Wen, J., Yu, L., Jiang, H., Xie, W., Xia, Y., et al. (2024) · Research Square · doi:10.21203/rs.3.rs-3871518/v1
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Dey, D., Biswas, S., Pal, S., Nandi, S., Khatun, N., Jha, R., Chakraborty, B. C., Baidya, A., Ghosh, R., Banerjee, S., et al. (2024) · SSRN Electronic Journal · doi:10.2139/ssrn.4867538
The temporal evolution of cancer hallmarksPreprint
Zapata, L., Gourmet, L. E., Lam, J. M., Ramazzotti, D., Pennycuick, A., Mallick, P., & Walker‐Samuel, S. (2024) · Research Square · doi:10.21203/rs.3.rs-5499335/v1
Role of immune checkpoint inhibitors in breast cancer and hematological malignancies
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“Furthermore, cellular deconvolution analysis revealed opposing in fi ltration patterns – plasma cell rich low-risk microenvironments versus Treg-dominated high-risk niches (Figure 6E), consistent with reported immune escape mechanisms [26].”
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Metadata
- Authors
- Alemohammad, H., Najafzadeh, B., Asadzadeh, Z., Baghbanzadeh, A., Ghorbaninezhad, F., Najafzadeh, A., Safarpour, H., Bernardini, R., Brunetti, O., Sonnessa, M., Fasano, R., Silvestris, N., & Baradaran, B.
- Affiliations
- University of Tabriz (IR)
- Tabriz University of Medical Sciences (IR)
- Birjand University of Medical Sciences (IR)
- University of Catania (IT)
- Istituto Tumori Bari (IT)
- Corresponding author
- Silvestris, Nicola
- Baradaran, Behzad
- ORCID
- Venue
- Biomedicine & Pharmacotherapy
- Publisher
- Elsevier BV
- Published
- 2022-02
- Volume
- 146
- Pages
- 112516
- ISSN
- 0753-3322 (ISSN-L)
- OpenAlex
- W4200317153
- Cited by
- 92
- References
- 240
- Citations by year
- 2026: 8 · 2025: 21 · 2024: 26 · 2023: 21 · 2022: 16
- FWCI
- 1.91
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Biomedicine & Pharmacotherapy (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- 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 checkpoint, cancer immunotherapy, immune checkpoint inhibitors, tumor immune evasion, CTLA-4, PD-1, TIM-3, TIGIT, LAG-3, regulatory T cells, myeloid-derived suppressor cells, regulatory B cells, dendritic cells, natural killer cells, monoclonal antibodies, microRNA, antitumor immunity
- MeSH terms
- Antineoplastic Agents, Immunological, Immune Checkpoint Inhibitors, Immune Checkpoint Proteins, Neoplasms, Monitoring, Immunologic, Signal Transduction, Down-Regulation, Up-Regulation, Tumor Escape, MicroRNAs
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