Recruitment, Infiltration, and Cytotoxicity of HLA-Independent Killer Lymphocytes in Three-Dimensional Melanoma Models
Cancer adoptive cell therapy (ACT) with HLA-independent tumor killer lymphocytes is a promising approach, with intrinsic features potentially addressing crucial tumor-escape mechanisms of checkpoint inhibitors. Cytokine-induced Killer (CIK) and Natural Killer (NK) lymphocytes share similar tumor-kil...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-05-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/10/2302 |
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| author | Ilenia Iaia Loretta Gammaitoni Giulia Cattaneo Lidia Giraudo Chiara Donini Erika Fiorino Luca Primo Fabrizio Carnevale-Schianca Massimo Aglietta Alberto Puliafito Dario Sangiolo |
| author_facet | Ilenia Iaia Loretta Gammaitoni Giulia Cattaneo Lidia Giraudo Chiara Donini Erika Fiorino Luca Primo Fabrizio Carnevale-Schianca Massimo Aglietta Alberto Puliafito Dario Sangiolo |
| author_sort | Ilenia Iaia |
| collection | DOAJ |
| description | Cancer adoptive cell therapy (ACT) with HLA-independent tumor killer lymphocytes is a promising approach, with intrinsic features potentially addressing crucial tumor-escape mechanisms of checkpoint inhibitors. Cytokine-induced Killer (CIK) and Natural Killer (NK) lymphocytes share similar tumor-killing mechanisms, with preclinical evidence of intense activity against multiple solid tumors and currently testing in clinical studies. To improve the effective clinical translation of such ACT approaches, several fundamental questions still need to be addressed within appropriate preclinical contexts, capable of overcoming limitations imposed by most traditional two-dimensional assays. Here, we developed a novel experimental approach to explore, dissect, and visualize the interactions of CIK and NK lymphocytes with melanoma tumors in vitro in 3D. Primary melanoma cells were assembled into small tumors that were dispersed in a 3D matrix and challenged with patient-derived CIK or the NK-92 cell line. By means of imaging-based methods, we reported, visualized, and quantitatively measured the recruitment of CIK and NK on the 3D targets, their infiltration, and cytotoxic activity. Our results support the effective tumor recruitment and tumor infiltration by CIK and NK. Such features appeared dependent on the specific geometric aspects of the environment but can be explained in terms of directional migration toward the tumor, without invoking major feedback components. Overall, our 3D platform allows us to monitor the processes of tumor recruitment, infiltration, and killing by means of live measurements, revealing important kinetic aspects of ACT with CIK and NK against melanoma. |
| first_indexed | 2024-03-10T11:30:27Z |
| format | Article |
| id | doaj.art-2fbde249aa354bacad66c0b92e7f5a65 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T11:30:27Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-2fbde249aa354bacad66c0b92e7f5a652023-11-21T19:14:58ZengMDPI AGCancers2072-66942021-05-011310230210.3390/cancers13102302Recruitment, Infiltration, and Cytotoxicity of HLA-Independent Killer Lymphocytes in Three-Dimensional Melanoma ModelsIlenia Iaia0Loretta Gammaitoni1Giulia Cattaneo2Lidia Giraudo3Chiara Donini4Erika Fiorino5Luca Primo6Fabrizio Carnevale-Schianca7Massimo Aglietta8Alberto Puliafito9Dario Sangiolo10Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, ItalyCandiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, ItalyCandiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, ItalyCandiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, ItalyCandiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, ItalyCandiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, ItalyCandiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, ItalyCandiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, ItalyCandiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, ItalyCandiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, ItalyCandiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, ItalyCancer adoptive cell therapy (ACT) with HLA-independent tumor killer lymphocytes is a promising approach, with intrinsic features potentially addressing crucial tumor-escape mechanisms of checkpoint inhibitors. Cytokine-induced Killer (CIK) and Natural Killer (NK) lymphocytes share similar tumor-killing mechanisms, with preclinical evidence of intense activity against multiple solid tumors and currently testing in clinical studies. To improve the effective clinical translation of such ACT approaches, several fundamental questions still need to be addressed within appropriate preclinical contexts, capable of overcoming limitations imposed by most traditional two-dimensional assays. Here, we developed a novel experimental approach to explore, dissect, and visualize the interactions of CIK and NK lymphocytes with melanoma tumors in vitro in 3D. Primary melanoma cells were assembled into small tumors that were dispersed in a 3D matrix and challenged with patient-derived CIK or the NK-92 cell line. By means of imaging-based methods, we reported, visualized, and quantitatively measured the recruitment of CIK and NK on the 3D targets, their infiltration, and cytotoxic activity. Our results support the effective tumor recruitment and tumor infiltration by CIK and NK. Such features appeared dependent on the specific geometric aspects of the environment but can be explained in terms of directional migration toward the tumor, without invoking major feedback components. Overall, our 3D platform allows us to monitor the processes of tumor recruitment, infiltration, and killing by means of live measurements, revealing important kinetic aspects of ACT with CIK and NK against melanoma.https://www.mdpi.com/2072-6694/13/10/23023D modelsmelanomacell therapyimaging |
| spellingShingle | Ilenia Iaia Loretta Gammaitoni Giulia Cattaneo Lidia Giraudo Chiara Donini Erika Fiorino Luca Primo Fabrizio Carnevale-Schianca Massimo Aglietta Alberto Puliafito Dario Sangiolo Recruitment, Infiltration, and Cytotoxicity of HLA-Independent Killer Lymphocytes in Three-Dimensional Melanoma Models Cancers 3D models melanoma cell therapy imaging |
| title | Recruitment, Infiltration, and Cytotoxicity of HLA-Independent Killer Lymphocytes in Three-Dimensional Melanoma Models |
| title_full | Recruitment, Infiltration, and Cytotoxicity of HLA-Independent Killer Lymphocytes in Three-Dimensional Melanoma Models |
| title_fullStr | Recruitment, Infiltration, and Cytotoxicity of HLA-Independent Killer Lymphocytes in Three-Dimensional Melanoma Models |
| title_full_unstemmed | Recruitment, Infiltration, and Cytotoxicity of HLA-Independent Killer Lymphocytes in Three-Dimensional Melanoma Models |
| title_short | Recruitment, Infiltration, and Cytotoxicity of HLA-Independent Killer Lymphocytes in Three-Dimensional Melanoma Models |
| title_sort | recruitment infiltration and cytotoxicity of hla independent killer lymphocytes in three dimensional melanoma models |
| topic | 3D models melanoma cell therapy imaging |
| url | https://www.mdpi.com/2072-6694/13/10/2302 |
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