Intratumoral interleukin-2/agonist CD40 antibody drives CD4+ - independent resolution of treated-turmors and CD4+ -dependent systemic and memory responses
Targeting interleukin-2 (IL-2) and/or agonist anti-CD40 antibody (Ab) into tumors represents an effective vaccination strategy that avoids systemic toxicity and resolves treated-site tumors. Here, we examined IL-2 and/or anti-CD40 Ab-driven local versus systemic T cell function and the installation...
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| Format: | Journal Article |
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Springer
2012
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| Online Access: | http://link.springer.de/link/service/journals/00262/index.htm http://hdl.handle.net/20.500.11937/49275 |
| _version_ | 1848758204487434240 |
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| author | Jackaman, Connie Nelson, Delia |
| author_facet | Jackaman, Connie Nelson, Delia |
| author_sort | Jackaman, Connie |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Targeting interleukin-2 (IL-2) and/or agonist anti-CD40 antibody (Ab) into tumors represents an effective vaccination strategy that avoids systemic toxicity and resolves treated-site tumors. Here, we examined IL-2 and/or anti-CD40 Ab-driven local versus systemic T cell function and the installation of T cell memory. Single tumor studies showed that IL-2 induced a potent CD4? and CD8? T cell response that was limited to the draining lymph node and treated-site tumor, and lymph node tumorspecific CD8? T cells did not upregulate CD44. A twotumor model showed that while IL-2-treated-site tumors resolved, distal tumors continued to grow, implying limited systemic immunity. In contrast, anti-CD40 Ab treatment with or without IL-2 expanded the systemic T cell response to non-draining lymph nodes, and distal tumors resolved. Tumor-specific T cells in lymph nodes of anti-CD40 Ab ± IL-2-treated mice upregulated CD44, demonstrating activation and transition to effector/memory migratory cells. While CD40-activated CD4? T cells were not required for eradicating treated-site tumors, they, plus CD8? T cells, were crucial for removing distal tumors. Rechallenge/depletion experiments showed that the effector/memory phase required the presence of previously CD40/IL-2-activated CD4? and CD8? T cells to prevent recurrence. These novel findings show that different T cell effector mechanisms can operate for the eradication of local treated-site tumors versus untreated distal tumors and that signaling through CD40 generates a whole of body, effector/memory CD4? and CD8? T cell response that is amplified and prolonged via IL-2. Thus, successful immunotherapy needs to generate collaborating CD4? and CD8? T cells for a complete long-term protective cure. |
| first_indexed | 2025-11-14T09:40:16Z |
| format | Journal Article |
| id | curtin-20.500.11937-49275 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T09:40:16Z |
| publishDate | 2012 |
| publisher | Springer |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-492752017-03-15T22:55:44Z Intratumoral interleukin-2/agonist CD40 antibody drives CD4+ - independent resolution of treated-turmors and CD4+ -dependent systemic and memory responses Jackaman, Connie Nelson, Delia Tumor immunity Memory CD8? T cells CD4? T cells Targeting interleukin-2 (IL-2) and/or agonist anti-CD40 antibody (Ab) into tumors represents an effective vaccination strategy that avoids systemic toxicity and resolves treated-site tumors. Here, we examined IL-2 and/or anti-CD40 Ab-driven local versus systemic T cell function and the installation of T cell memory. Single tumor studies showed that IL-2 induced a potent CD4? and CD8? T cell response that was limited to the draining lymph node and treated-site tumor, and lymph node tumorspecific CD8? T cells did not upregulate CD44. A twotumor model showed that while IL-2-treated-site tumors resolved, distal tumors continued to grow, implying limited systemic immunity. In contrast, anti-CD40 Ab treatment with or without IL-2 expanded the systemic T cell response to non-draining lymph nodes, and distal tumors resolved. Tumor-specific T cells in lymph nodes of anti-CD40 Ab ± IL-2-treated mice upregulated CD44, demonstrating activation and transition to effector/memory migratory cells. While CD40-activated CD4? T cells were not required for eradicating treated-site tumors, they, plus CD8? T cells, were crucial for removing distal tumors. Rechallenge/depletion experiments showed that the effector/memory phase required the presence of previously CD40/IL-2-activated CD4? and CD8? T cells to prevent recurrence. These novel findings show that different T cell effector mechanisms can operate for the eradication of local treated-site tumors versus untreated distal tumors and that signaling through CD40 generates a whole of body, effector/memory CD4? and CD8? T cell response that is amplified and prolonged via IL-2. Thus, successful immunotherapy needs to generate collaborating CD4? and CD8? T cells for a complete long-term protective cure. 2012 Journal Article http://hdl.handle.net/20.500.11937/49275 http://link.springer.de/link/service/journals/00262/index.htm Springer restricted |
| spellingShingle | Tumor immunity Memory CD8? T cells CD4? T cells Jackaman, Connie Nelson, Delia Intratumoral interleukin-2/agonist CD40 antibody drives CD4+ - independent resolution of treated-turmors and CD4+ -dependent systemic and memory responses |
| title | Intratumoral interleukin-2/agonist CD40 antibody drives CD4+ - independent resolution of treated-turmors and CD4+ -dependent systemic and memory responses |
| title_full | Intratumoral interleukin-2/agonist CD40 antibody drives CD4+ - independent resolution of treated-turmors and CD4+ -dependent systemic and memory responses |
| title_fullStr | Intratumoral interleukin-2/agonist CD40 antibody drives CD4+ - independent resolution of treated-turmors and CD4+ -dependent systemic and memory responses |
| title_full_unstemmed | Intratumoral interleukin-2/agonist CD40 antibody drives CD4+ - independent resolution of treated-turmors and CD4+ -dependent systemic and memory responses |
| title_short | Intratumoral interleukin-2/agonist CD40 antibody drives CD4+ - independent resolution of treated-turmors and CD4+ -dependent systemic and memory responses |
| title_sort | intratumoral interleukin-2/agonist cd40 antibody drives cd4+ - independent resolution of treated-turmors and cd4+ -dependent systemic and memory responses |
| topic | Tumor immunity Memory CD8? T cells CD4? T cells |
| url | http://link.springer.de/link/service/journals/00262/index.htm http://hdl.handle.net/20.500.11937/49275 |