Targeting Potential of Innate Lymphoid Cells in Melanoma and Other Cancers
Abstract
:1. Introduction
2. Characteristics of ILCs
3. ILCs and the Immune Response to Tumors
4. ILCs and Immune Checkpoint Molecules
4.1. PD-1 Expression Patterns
Population | Mouse Expression | Human Expression | Function | References |
---|---|---|---|---|
NK cells | Expressed particularly on tumor infiltrating populations | Negative regulator | [28,100,101,102,103,104,105,106,107,108] | |
ILC1s | Low level at steady state ILC1-subsets in tumors express intermediate levels | High levels in tumor infiltrating populations Expressed in PBMCs of cancer patients | Potential inhibitory role | [28,51,97] |
ILC2s | Expressed in tumor infiltrating populations 20–40% of lung ILC2s, increases upon inflammation Substantially expressed in the colon | Significantly expressed in tumor-infiltrating populations Expressed in PBMCs of cancer patients | Regulates airway hypersensitivity Negative regulator of ILC2 function | [28,60,62,99,111,113,114,115,116,117,118,119] |
ILC3s | Expressed in mouse lung, colon, decidual tissues Expressed substantially on LTi cells residing in the colon and in other gut tissues, upregulated upon activation | Expressed in the decidua Expressed in breast and GI tumors Low expression in PBMCs of cancer patients | Mediating immune tolerance during pregnancy Promoting metabolism and maintaining barrier function in the intestine Potential inhibitory role in cancer | [28,97,120,121] |
4.2. Immune Checkpoint Targeting Potential of ILCs
5. Novel ILC Targeting Approaches in Cancer
5.1. Targeting Cytokines and Their Receptors
5.2. Influencing ILC Plasticity and Transdifferentiation
5.3. ILC Differentiation, Expansion, and Engineering: Chimeric Antigen Receptors and TCRs
5.4. Bi- and Tri-Specific Vectors
5.5. Potential of ILC-Based Immunotherapies in Melanoma
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Antibody | Target | FDA Approval with Initial Indication | Subsequent Indications | References |
---|---|---|---|---|
ipilimumab | CTLA-4 | 2011 for unresectable or metastatic melanoma | melanoma (alone or w/nivolumab) other solid tumors (w/nivolumab) | [77,78] |
tremelimumab | CTLA-4 | 2022 for unresectable HCC (w/durvalumab), and metastatic NSCLC (w/durvalumab and platinum-based chemotherapy) | [79] | |
pembrolizumab | PD-1 | 2014 (accelerated) for unresectable or metastatic melanoma 2015 (accelerated) for metastatic NSCLC | many solid tumors cHL, PMBCL | [78,80,81] |
nivolumab | PD-1 | 2014 (accelerated) for unresectable or metastatic melanoma 2015 for advanced RCC and metastatic squamous and non-squamous NSCLC 2016 (accelerated) for relapsed or progressive cHL | many solid tumors | [78,82,83,84,85] |
cemiplimab | PD-1 | 2018 for locally advanced or metastatic CSCC | BCC, NSCLC | [86,87,88] |
dostarlimab | PD-1 | 2021 (accelerated) for dMMR recurrent or advanced endometrial cancer | [89] | |
atezolizumab | PD-L1 | 2016 (accelerated) for locally advanced or metastatic urothelial carcinoma 2016 for metastatic NSCLC | other solid tumors | [78,90,91] |
avelumab | PD-L1 | 2017 (accelerated) for metastatic MCC and locally advanced or metastatic urothelial carcinoma | RCC | [78,92,93] |
durvalumab | PD-L1 | 2017 (accelerated) for locally advanced or metastatic urothelial carcinoma | NSCLC, SCLC, BTC | [78,94] |
relatlimab | LAG-3 | 2022 for unresectable or metastatic melanoma (w/nivolumab, market name Opdualag) | [95] |
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Seo, H.; Verma, A.; Kinzel, M.; Huang, Q.; Mahoney, D.J.; Jacquelot, N. Targeting Potential of Innate Lymphoid Cells in Melanoma and Other Cancers. Pharmaceutics 2023, 15, 2001. https://doi.org/10.3390/pharmaceutics15072001
Seo H, Verma A, Kinzel M, Huang Q, Mahoney DJ, Jacquelot N. Targeting Potential of Innate Lymphoid Cells in Melanoma and Other Cancers. Pharmaceutics. 2023; 15(7):2001. https://doi.org/10.3390/pharmaceutics15072001
Chicago/Turabian StyleSeo, Hobin, Amisha Verma, Megan Kinzel, Qiutong Huang, Douglas J. Mahoney, and Nicolas Jacquelot. 2023. "Targeting Potential of Innate Lymphoid Cells in Melanoma and Other Cancers" Pharmaceutics 15, no. 7: 2001. https://doi.org/10.3390/pharmaceutics15072001
APA StyleSeo, H., Verma, A., Kinzel, M., Huang, Q., Mahoney, D. J., & Jacquelot, N. (2023). Targeting Potential of Innate Lymphoid Cells in Melanoma and Other Cancers. Pharmaceutics, 15(7), 2001. https://doi.org/10.3390/pharmaceutics15072001