A possible new pathway in natural killer cell activation also reveals the difficulty in determining human NK cell function in cancer
Abstract Immunotherapy is rapidly becoming the fourth arm of cancer treatment, and breakthrough successes have been observed in multiple malignancies. However, despite the potential for impressive anti-tumor effects, on average, only 25% of patients respond, and barriers clearly remain. Hence, uncov...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2018-08-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s40425-018-0392-0 |
| _version_ | 1818548347100725248 |
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| author | Robert J. Canter William J. Murphy |
| author_facet | Robert J. Canter William J. Murphy |
| author_sort | Robert J. Canter |
| collection | DOAJ |
| description | Abstract Immunotherapy is rapidly becoming the fourth arm of cancer treatment, and breakthrough successes have been observed in multiple malignancies. However, despite the potential for impressive anti-tumor effects, on average, only 25% of patients respond, and barriers clearly remain. Hence, uncovering innovative ways to apply immunotherapy and overcome immune resistance remains an unmet need in immuno-oncology. Natural killer (NK) cells are an attractive candidate for extending the promise of immunotherapy, although success to date has been largely limited to hematological cancers. An important study has identified novel ways in which NK cells sense and respond to tumors, and these findings may impact clinical translation of NK cells in cancer immunotherapy. Using the activating receptor NKp44, NK cells were shown to bind platelet-derived growth factor DD (PDGF-DD) which was secreted by tumors. Using transgenic mice, NKp44 binding of tumor-expressed PDGF-DD was able to limit tumor growth, and expression of natural cytotoxicity receptor-associated gene signatures (of which NKp44 is a member) was correlated to clinical outcomes. This study highlights the potential for effector-target interactions to impact immune homeostasis in previously unrecognized ways, while at the same time, underscoring the complexities inherent in pre-clinical/ translational experimental design which may confound clinical application of these interesting results. |
| first_indexed | 2024-12-12T08:18:43Z |
| format | Article |
| id | doaj.art-0af1e88149d941758a5e8db5fb361d8b |
| institution | Directory Open Access Journal |
| issn | 2051-1426 |
| language | English |
| last_indexed | 2024-12-12T08:18:43Z |
| publishDate | 2018-08-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj.art-0af1e88149d941758a5e8db5fb361d8b2022-12-22T00:31:29ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262018-08-01611310.1186/s40425-018-0392-0A possible new pathway in natural killer cell activation also reveals the difficulty in determining human NK cell function in cancerRobert J. Canter0William J. Murphy1Department of Surgery, Division of Surgical Oncology, University of California Davis Medical CenterDistinguished Professor of Dermatology and Internal Medicine, University of California Davis Medical CenterAbstract Immunotherapy is rapidly becoming the fourth arm of cancer treatment, and breakthrough successes have been observed in multiple malignancies. However, despite the potential for impressive anti-tumor effects, on average, only 25% of patients respond, and barriers clearly remain. Hence, uncovering innovative ways to apply immunotherapy and overcome immune resistance remains an unmet need in immuno-oncology. Natural killer (NK) cells are an attractive candidate for extending the promise of immunotherapy, although success to date has been largely limited to hematological cancers. An important study has identified novel ways in which NK cells sense and respond to tumors, and these findings may impact clinical translation of NK cells in cancer immunotherapy. Using the activating receptor NKp44, NK cells were shown to bind platelet-derived growth factor DD (PDGF-DD) which was secreted by tumors. Using transgenic mice, NKp44 binding of tumor-expressed PDGF-DD was able to limit tumor growth, and expression of natural cytotoxicity receptor-associated gene signatures (of which NKp44 is a member) was correlated to clinical outcomes. This study highlights the potential for effector-target interactions to impact immune homeostasis in previously unrecognized ways, while at the same time, underscoring the complexities inherent in pre-clinical/ translational experimental design which may confound clinical application of these interesting results.http://link.springer.com/article/10.1186/s40425-018-0392-0Natural killer cellsPlatelet-derived growth factorNKp44TCGAImmunotherapy |
| spellingShingle | Robert J. Canter William J. Murphy A possible new pathway in natural killer cell activation also reveals the difficulty in determining human NK cell function in cancer Journal for ImmunoTherapy of Cancer Natural killer cells Platelet-derived growth factor NKp44 TCGA Immunotherapy |
| title | A possible new pathway in natural killer cell activation also reveals the difficulty in determining human NK cell function in cancer |
| title_full | A possible new pathway in natural killer cell activation also reveals the difficulty in determining human NK cell function in cancer |
| title_fullStr | A possible new pathway in natural killer cell activation also reveals the difficulty in determining human NK cell function in cancer |
| title_full_unstemmed | A possible new pathway in natural killer cell activation also reveals the difficulty in determining human NK cell function in cancer |
| title_short | A possible new pathway in natural killer cell activation also reveals the difficulty in determining human NK cell function in cancer |
| title_sort | possible new pathway in natural killer cell activation also reveals the difficulty in determining human nk cell function in cancer |
| topic | Natural killer cells Platelet-derived growth factor NKp44 TCGA Immunotherapy |
| url | http://link.springer.com/article/10.1186/s40425-018-0392-0 |
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