Elicitation of stem-like CD8+ T cell responses via lymph node-targeted chemoimmunotherapy evokes systemic tumor control
Background Tumor-draining lymph nodes (TdLNs) are critical in the regulation of local and systemic antitumor T cell immunity and are implicated in coordinating responses to immunomodulatory therapies.Methods Biomaterial nanoparticles that deliver chemotherapeutic drug paclitaxel to TdLNs were levera...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2022-09-01
|
| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/10/9/e005079.full |
| _version_ | 1798019337881124864 |
|---|---|
| author | Margaret P Manspeaker Meghan J O'Melia Susan N Thomas |
| author_facet | Margaret P Manspeaker Meghan J O'Melia Susan N Thomas |
| author_sort | Margaret P Manspeaker |
| collection | DOAJ |
| description | Background Tumor-draining lymph nodes (TdLNs) are critical in the regulation of local and systemic antitumor T cell immunity and are implicated in coordinating responses to immunomodulatory therapies.Methods Biomaterial nanoparticles that deliver chemotherapeutic drug paclitaxel to TdLNs were leveraged to explore its effects in combination and immune checkpoint blockade (ICB) antibody immunotherapy to determine the benefit of TdLN-directed chemoimmunotherapy on tumor control.Results Accumulation of immunotherapeutic drugs in combination within TdLNs synergistically enhanced systemic T cell responses that led to improved control of local and disseminated disease and enhanced survival in multiple murine breast tumor models.Conclusions These findings suggest a previously underappreciated role of secondary lymphoid tissues in mediating effects of chemoimmunotherapy and demonstrate the potential for nanotechnology to unleashing drug synergies via lymph node targeted delivery to elicit improved response of breast and other cancers. |
| first_indexed | 2024-04-11T16:39:03Z |
| format | Article |
| id | doaj.art-3fa5f1ebad2d4f6a9079cdc62f66252e |
| institution | Directory Open Access Journal |
| issn | 2051-1426 |
| language | English |
| last_indexed | 2024-04-11T16:39:03Z |
| publishDate | 2022-09-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj.art-3fa5f1ebad2d4f6a9079cdc62f66252e2022-12-22T04:13:43ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262022-09-0110910.1136/jitc-2022-005079Elicitation of stem-like CD8+ T cell responses via lymph node-targeted chemoimmunotherapy evokes systemic tumor controlMargaret P Manspeaker0Meghan J O'Melia1Susan N Thomas2Parker H. Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, USAWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USAParker H. Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, USABackground Tumor-draining lymph nodes (TdLNs) are critical in the regulation of local and systemic antitumor T cell immunity and are implicated in coordinating responses to immunomodulatory therapies.Methods Biomaterial nanoparticles that deliver chemotherapeutic drug paclitaxel to TdLNs were leveraged to explore its effects in combination and immune checkpoint blockade (ICB) antibody immunotherapy to determine the benefit of TdLN-directed chemoimmunotherapy on tumor control.Results Accumulation of immunotherapeutic drugs in combination within TdLNs synergistically enhanced systemic T cell responses that led to improved control of local and disseminated disease and enhanced survival in multiple murine breast tumor models.Conclusions These findings suggest a previously underappreciated role of secondary lymphoid tissues in mediating effects of chemoimmunotherapy and demonstrate the potential for nanotechnology to unleashing drug synergies via lymph node targeted delivery to elicit improved response of breast and other cancers.https://jitc.bmj.com/content/10/9/e005079.full |
| spellingShingle | Margaret P Manspeaker Meghan J O'Melia Susan N Thomas Elicitation of stem-like CD8+ T cell responses via lymph node-targeted chemoimmunotherapy evokes systemic tumor control Journal for ImmunoTherapy of Cancer |
| title | Elicitation of stem-like CD8+ T cell responses via lymph node-targeted chemoimmunotherapy evokes systemic tumor control |
| title_full | Elicitation of stem-like CD8+ T cell responses via lymph node-targeted chemoimmunotherapy evokes systemic tumor control |
| title_fullStr | Elicitation of stem-like CD8+ T cell responses via lymph node-targeted chemoimmunotherapy evokes systemic tumor control |
| title_full_unstemmed | Elicitation of stem-like CD8+ T cell responses via lymph node-targeted chemoimmunotherapy evokes systemic tumor control |
| title_short | Elicitation of stem-like CD8+ T cell responses via lymph node-targeted chemoimmunotherapy evokes systemic tumor control |
| title_sort | elicitation of stem like cd8 t cell responses via lymph node targeted chemoimmunotherapy evokes systemic tumor control |
| url | https://jitc.bmj.com/content/10/9/e005079.full |
| work_keys_str_mv | AT margaretpmanspeaker elicitationofstemlikecd8tcellresponsesvialymphnodetargetedchemoimmunotherapyevokessystemictumorcontrol AT meghanjomelia elicitationofstemlikecd8tcellresponsesvialymphnodetargetedchemoimmunotherapyevokessystemictumorcontrol AT susannthomas elicitationofstemlikecd8tcellresponsesvialymphnodetargetedchemoimmunotherapyevokessystemictumorcontrol |