Vinorelbine and Intermittent Cyclophosphamide Sensitize an Aggressive Myc-Driven B-Cell Lymphoma to Anti-PD-1 by an Immunological Memory Effective against Tumor Re-Challenge
We have previously shown in triple-negative breast cancer (TNBC) models that a triple therapy (TT) including intermittent cyclophosphamide (C), vinorelbine (V), and anti-PD-1 activates antigen-presenting cells (APC) and generates stem like-T cells able to control local and metastatic tumor progressi...
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| Format: | Article |
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MDPI AG
2023-03-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/12/7/2535 |
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| author | Stefania Orecchioni Paolo Falvo Giovanna Talarico Giulia Mitola Giulia Bravetti Patrizia Mancuso Paola Nicoli Francesco Bertolini |
| author_facet | Stefania Orecchioni Paolo Falvo Giovanna Talarico Giulia Mitola Giulia Bravetti Patrizia Mancuso Paola Nicoli Francesco Bertolini |
| author_sort | Stefania Orecchioni |
| collection | DOAJ |
| description | We have previously shown in triple-negative breast cancer (TNBC) models that a triple therapy (TT) including intermittent cyclophosphamide (C), vinorelbine (V), and anti-PD-1 activates antigen-presenting cells (APC) and generates stem like-T cells able to control local and metastatic tumor progression. In the present manuscript, we report the generation of a highly aggressive, anti-PD-1 resistant model of a high-grade, Myc-driven B-cell non-Hodgkin’s lymphoma (NHL) that can be controlled in vivo by TT but not by other chemotherapeutic agents, including cytarabine (AraC), platinum (P), and doxorubicin (D). The immunological memory elicited in tumor-bearing mice by TT (but not by other treatments) can effectively control NHL re-challenge even at very high inoculum doses. TT re-shaped the landscape of circulating innate NK cells and adaptive immune cells, including B and T cells, and significantly reduced exhausted CD4<sup>+</sup> and CD8<sup>+</sup> TIM3<sup>+</sup>PD-1<sup>+</sup> T cells in the spleens of treated mice. |
| first_indexed | 2024-03-11T05:32:43Z |
| format | Article |
| id | doaj.art-560e31b84fb64af3b64940093455bad2 |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-11T05:32:43Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-560e31b84fb64af3b64940093455bad22023-11-17T16:58:26ZengMDPI AGJournal of Clinical Medicine2077-03832023-03-01127253510.3390/jcm12072535Vinorelbine and Intermittent Cyclophosphamide Sensitize an Aggressive Myc-Driven B-Cell Lymphoma to Anti-PD-1 by an Immunological Memory Effective against Tumor Re-ChallengeStefania Orecchioni0Paolo Falvo1Giovanna Talarico2Giulia Mitola3Giulia Bravetti4Patrizia Mancuso5Paola Nicoli6Francesco Bertolini7Laboratory of Hematology-Oncology, European Institute of Oncology IRCCS, Via Ripamonti 435, 20141 Milan, ItalyLaboratory of Hematology-Oncology, European Institute of Oncology IRCCS, Via Ripamonti 435, 20141 Milan, ItalyLaboratory of Hematology-Oncology, European Institute of Oncology IRCCS, Via Ripamonti 435, 20141 Milan, ItalyLaboratory of Hematology-Oncology, European Institute of Oncology IRCCS, Via Ripamonti 435, 20141 Milan, ItalyLaboratory of Hematology-Oncology, European Institute of Oncology IRCCS, Via Ripamonti 435, 20141 Milan, ItalyLaboratory of Hematology-Oncology, European Institute of Oncology IRCCS, Via Ripamonti 435, 20141 Milan, ItalyDepartment of Experimental Oncology, European Institute of Oncology IRCCS, Via Adamello 16, 20137 Milan, ItalyLaboratory of Hematology-Oncology, European Institute of Oncology IRCCS, Via Ripamonti 435, 20141 Milan, ItalyWe have previously shown in triple-negative breast cancer (TNBC) models that a triple therapy (TT) including intermittent cyclophosphamide (C), vinorelbine (V), and anti-PD-1 activates antigen-presenting cells (APC) and generates stem like-T cells able to control local and metastatic tumor progression. In the present manuscript, we report the generation of a highly aggressive, anti-PD-1 resistant model of a high-grade, Myc-driven B-cell non-Hodgkin’s lymphoma (NHL) that can be controlled in vivo by TT but not by other chemotherapeutic agents, including cytarabine (AraC), platinum (P), and doxorubicin (D). The immunological memory elicited in tumor-bearing mice by TT (but not by other treatments) can effectively control NHL re-challenge even at very high inoculum doses. TT re-shaped the landscape of circulating innate NK cells and adaptive immune cells, including B and T cells, and significantly reduced exhausted CD4<sup>+</sup> and CD8<sup>+</sup> TIM3<sup>+</sup>PD-1<sup>+</sup> T cells in the spleens of treated mice.https://www.mdpi.com/2077-0383/12/7/2535lymphomacyclophosphamidevinorelbinemetronomic chemotherapycheckpoint inhibitors |
| spellingShingle | Stefania Orecchioni Paolo Falvo Giovanna Talarico Giulia Mitola Giulia Bravetti Patrizia Mancuso Paola Nicoli Francesco Bertolini Vinorelbine and Intermittent Cyclophosphamide Sensitize an Aggressive Myc-Driven B-Cell Lymphoma to Anti-PD-1 by an Immunological Memory Effective against Tumor Re-Challenge Journal of Clinical Medicine lymphoma cyclophosphamide vinorelbine metronomic chemotherapy checkpoint inhibitors |
| title | Vinorelbine and Intermittent Cyclophosphamide Sensitize an Aggressive Myc-Driven B-Cell Lymphoma to Anti-PD-1 by an Immunological Memory Effective against Tumor Re-Challenge |
| title_full | Vinorelbine and Intermittent Cyclophosphamide Sensitize an Aggressive Myc-Driven B-Cell Lymphoma to Anti-PD-1 by an Immunological Memory Effective against Tumor Re-Challenge |
| title_fullStr | Vinorelbine and Intermittent Cyclophosphamide Sensitize an Aggressive Myc-Driven B-Cell Lymphoma to Anti-PD-1 by an Immunological Memory Effective against Tumor Re-Challenge |
| title_full_unstemmed | Vinorelbine and Intermittent Cyclophosphamide Sensitize an Aggressive Myc-Driven B-Cell Lymphoma to Anti-PD-1 by an Immunological Memory Effective against Tumor Re-Challenge |
| title_short | Vinorelbine and Intermittent Cyclophosphamide Sensitize an Aggressive Myc-Driven B-Cell Lymphoma to Anti-PD-1 by an Immunological Memory Effective against Tumor Re-Challenge |
| title_sort | vinorelbine and intermittent cyclophosphamide sensitize an aggressive myc driven b cell lymphoma to anti pd 1 by an immunological memory effective against tumor re challenge |
| topic | lymphoma cyclophosphamide vinorelbine metronomic chemotherapy checkpoint inhibitors |
| url | https://www.mdpi.com/2077-0383/12/7/2535 |
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