Predicting the response to CTLA-4 blockade by longitudinal noninvasive monitoring of CD8 T cells
Immunotherapy using checkpoint-blocking antibodies against targets such as CTLA-4 and PD-1 can cure melanoma and non-small cell lung cancer in a subset of patients. The presence of CD8 T cells in the tumor correlates with improved survival. We show that immuno-positron emission tomography (immuno-PE...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
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Rockefeller University Press
2018
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| Online Access: | http://hdl.handle.net/1721.1/115202 https://orcid.org/0000-0002-0895-3557 https://orcid.org/0000-0002-1090-6071 |
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| author | Rashidian, Mohammad Ingram, Jessica R. Dougan, Michael Dongre, Anushka Whang, Katherine A. LeGall, Camille Cragnolini, Juan J. Bierie, Brian Gostissa, Monica Gorman, James Grotenbreg, Gijsbert M. Bhan, Atul Weinberg, Robert A Ploegh, Hidde |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Rashidian, Mohammad Ingram, Jessica R. Dougan, Michael Dongre, Anushka Whang, Katherine A. LeGall, Camille Cragnolini, Juan J. Bierie, Brian Gostissa, Monica Gorman, James Grotenbreg, Gijsbert M. Bhan, Atul Weinberg, Robert A Ploegh, Hidde |
| author_sort | Rashidian, Mohammad |
| collection | MIT |
| description | Immunotherapy using checkpoint-blocking antibodies against targets such as CTLA-4 and PD-1 can cure melanoma and non-small cell lung cancer in a subset of patients. The presence of CD8 T cells in the tumor correlates with improved survival. We show that immuno-positron emission tomography (immuno-PET) can visualize tumors by detecting infiltrating lymphocytes and, through longitudinal observation of individual animals, distinguish responding tumors from those that do not respond to therapy. We used 89 Zr-labeled PEGylated single-domain antibody fragments (VHHs) specific for CD8 to track the presence of intratumoral CD8 + T cells in the immunotherapy-susceptible B16 melanoma model in response to checkpoint blockade. A 89 Zr-labeled PEGylated anti-CD8 VHH detected thymus and secondary lymphoid structures as well as intratumoral CD8 T cells. Animals that responded to CTLA-4 therapy showed a homogeneous distribution of the anti-CD8 PET signal throughout the tumor, whereas more heterogeneous infiltration of CD8 T cells correlated with faster tumor growth and worse responses. To support the validity of these observations, we used two different transplantable breast cancer models, yielding results that conformed with predictions based on the antimelanoma response. It may thus be possible to use immuno-PET and monitor antitumor immune responses as a prognostic tool to predict patient responses to checkpoint therapies. |
| first_indexed | 2024-09-23T15:13:15Z |
| format | Article |
| id | mit-1721.1/115202 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T15:13:15Z |
| publishDate | 2018 |
| publisher | Rockefeller University Press |
| record_format | dspace |
| spelling | mit-1721.1/1152022022-10-02T01:28:35Z Predicting the response to CTLA-4 blockade by longitudinal noninvasive monitoring of CD8 T cells Rashidian, Mohammad Ingram, Jessica R. Dougan, Michael Dongre, Anushka Whang, Katherine A. LeGall, Camille Cragnolini, Juan J. Bierie, Brian Gostissa, Monica Gorman, James Grotenbreg, Gijsbert M. Bhan, Atul Weinberg, Robert A Ploegh, Hidde Massachusetts Institute of Technology. Department of Biology Weinberg, Robert A Ploegh, Hidde Immunotherapy using checkpoint-blocking antibodies against targets such as CTLA-4 and PD-1 can cure melanoma and non-small cell lung cancer in a subset of patients. The presence of CD8 T cells in the tumor correlates with improved survival. We show that immuno-positron emission tomography (immuno-PET) can visualize tumors by detecting infiltrating lymphocytes and, through longitudinal observation of individual animals, distinguish responding tumors from those that do not respond to therapy. We used 89 Zr-labeled PEGylated single-domain antibody fragments (VHHs) specific for CD8 to track the presence of intratumoral CD8 + T cells in the immunotherapy-susceptible B16 melanoma model in response to checkpoint blockade. A 89 Zr-labeled PEGylated anti-CD8 VHH detected thymus and secondary lymphoid structures as well as intratumoral CD8 T cells. Animals that responded to CTLA-4 therapy showed a homogeneous distribution of the anti-CD8 PET signal throughout the tumor, whereas more heterogeneous infiltration of CD8 T cells correlated with faster tumor growth and worse responses. To support the validity of these observations, we used two different transplantable breast cancer models, yielding results that conformed with predictions based on the antimelanoma response. It may thus be possible to use immuno-PET and monitor antitumor immune responses as a prognostic tool to predict patient responses to checkpoint therapies. National Institutes of Health (U.S.) (Grant R01-AI087879-06) National Institutes of Health (U.S.) (Grant DP1-GM106409-03) National Institutes of Health (U.S.) (Grant R01-GM100518-04) National Institutes of Health (U.S.) (Grant P01 CA080111) 2018-05-02T20:37:26Z 2018-05-02T20:37:26Z 2017-06 2017-03 2018-02-23T15:36:34Z Article http://purl.org/eprint/type/JournalArticle 0022-1007 1540-9538 http://hdl.handle.net/1721.1/115202 Rashidian, Mohammad et al. “Predicting the Response to CTLA-4 Blockade by Longitudinal Noninvasive Monitoring of CD8 T Cells.” The Journal of Experimental Medicine 214, 8 (June 2017): 2243–2255 © 2017 Rashidian et al https://orcid.org/0000-0002-0895-3557 https://orcid.org/0000-0002-1090-6071 http://dx.doi.org/10.1084/JEM.20161950 Journal of Experimental Medicine Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) https://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Rockefeller University Press Rockefeller University Press |
| spellingShingle | Rashidian, Mohammad Ingram, Jessica R. Dougan, Michael Dongre, Anushka Whang, Katherine A. LeGall, Camille Cragnolini, Juan J. Bierie, Brian Gostissa, Monica Gorman, James Grotenbreg, Gijsbert M. Bhan, Atul Weinberg, Robert A Ploegh, Hidde Predicting the response to CTLA-4 blockade by longitudinal noninvasive monitoring of CD8 T cells |
| title | Predicting the response to CTLA-4 blockade by longitudinal noninvasive monitoring of CD8 T cells |
| title_full | Predicting the response to CTLA-4 blockade by longitudinal noninvasive monitoring of CD8 T cells |
| title_fullStr | Predicting the response to CTLA-4 blockade by longitudinal noninvasive monitoring of CD8 T cells |
| title_full_unstemmed | Predicting the response to CTLA-4 blockade by longitudinal noninvasive monitoring of CD8 T cells |
| title_short | Predicting the response to CTLA-4 blockade by longitudinal noninvasive monitoring of CD8 T cells |
| title_sort | predicting the response to ctla 4 blockade by longitudinal noninvasive monitoring of cd8 t cells |
| url | http://hdl.handle.net/1721.1/115202 https://orcid.org/0000-0002-0895-3557 https://orcid.org/0000-0002-1090-6071 |
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