Distinct predictive biomarker candidates for response to anti-CTLA-4 and anti-PD-1 immunotherapy in melanoma patients
Abstract Background While immune checkpoint blockade has greatly improved clinical outcomes in diseases such as melanoma, there remains a need for predictive biomarkers to determine who will likely benefit most from which therapy. To date, most biomarkers of response have been identified in the tumo...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2018-03-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | http://link.springer.com/article/10.1186/s40425-018-0328-8 |
| _version_ | 1819021389758201856 |
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| author | Priyanka B. Subrahmanyam Zhiwan Dong Daniel Gusenleitner Anita Giobbie-Hurder Mariano Severgnini Jun Zhou Michael Manos Lauren M. Eastman Holden T. Maecker F. Stephen Hodi |
| author_facet | Priyanka B. Subrahmanyam Zhiwan Dong Daniel Gusenleitner Anita Giobbie-Hurder Mariano Severgnini Jun Zhou Michael Manos Lauren M. Eastman Holden T. Maecker F. Stephen Hodi |
| author_sort | Priyanka B. Subrahmanyam |
| collection | DOAJ |
| description | Abstract Background While immune checkpoint blockade has greatly improved clinical outcomes in diseases such as melanoma, there remains a need for predictive biomarkers to determine who will likely benefit most from which therapy. To date, most biomarkers of response have been identified in the tumors themselves. Biomarkers that could be assessed from peripheral blood would be even more desirable, because of ease of access and reproducibility of sampling. Methods We used mass cytometry (CyTOF) to comprehensively profile peripheral blood of melanoma patients, in order to find predictive biomarkers of response to anti-CTLA-4 or anti-PD-1 therapy. Using a panel of ~ 40 surface and intracellular markers, we performed in-depth phenotypic and functional immune profiling to identify potential predictive biomarker candidates. Results Immune profiling of baseline peripheral blood samples using CyTOF revealed that anti-CTLA-4 and anti-PD-1 therapies have distinct sets of candidate biomarkers. The distribution of CD4+ and CD8+ memory/non-memory cells and other memory subsets was different between responders and non-responders to anti-CTLA-4 therapy. In anti-PD-1 (but not anti-CTLA-4) treated patients, we discovered differences in CD69 and MIP-1β expressing NK cells between responders and non-responders. Finally, multivariate analysis was used to develop a model for the prediction of response. Conclusions Our results indicate that anti-CTLA-4 and anti-PD-1 have distinct predictive biomarker candidates. CD4+ and CD8+ memory T cell subsets play an important role in response to anti-CTLA-4, and are potential biomarker candidates. For anti-PD-1 therapy, NK cell subsets (but not memory T cell subsets) correlated with clinical response to therapy. These functionally active NK cell subsets likely play a critical role in the anti-tumor response triggered by anti-PD-1. |
| first_indexed | 2024-12-21T04:06:20Z |
| format | Article |
| id | doaj.art-0b4e970d2cb54a8e9cd3f79ea9e5e8c9 |
| institution | Directory Open Access Journal |
| issn | 2051-1426 |
| language | English |
| last_indexed | 2024-12-21T04:06:20Z |
| publishDate | 2018-03-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj.art-0b4e970d2cb54a8e9cd3f79ea9e5e8c92022-12-21T19:16:34ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262018-03-016111410.1186/s40425-018-0328-8Distinct predictive biomarker candidates for response to anti-CTLA-4 and anti-PD-1 immunotherapy in melanoma patientsPriyanka B. Subrahmanyam0Zhiwan Dong1Daniel Gusenleitner2Anita Giobbie-Hurder3Mariano Severgnini4Jun Zhou5Michael Manos6Lauren M. Eastman7Holden T. Maecker8F. Stephen Hodi9Institute for Immunity, Transplantation, and Infection, Stanford University School of MedicineCenter for Immuno-oncology, Dana-Farber Cancer Institute and Harvard Medical SchoolCenter for Immuno-oncology, Dana-Farber Cancer Institute and Harvard Medical SchoolCenter for Immuno-oncology, Dana-Farber Cancer Institute and Harvard Medical SchoolCenter for Immuno-oncology, Dana-Farber Cancer Institute and Harvard Medical SchoolDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical SchoolCenter for Immuno-oncology, Dana-Farber Cancer Institute and Harvard Medical SchoolCenter for Immuno-oncology, Dana-Farber Cancer Institute and Harvard Medical SchoolInstitute for Immunity, Transplantation, and Infection, Stanford University School of MedicineCenter for Immuno-oncology, Dana-Farber Cancer Institute and Harvard Medical SchoolAbstract Background While immune checkpoint blockade has greatly improved clinical outcomes in diseases such as melanoma, there remains a need for predictive biomarkers to determine who will likely benefit most from which therapy. To date, most biomarkers of response have been identified in the tumors themselves. Biomarkers that could be assessed from peripheral blood would be even more desirable, because of ease of access and reproducibility of sampling. Methods We used mass cytometry (CyTOF) to comprehensively profile peripheral blood of melanoma patients, in order to find predictive biomarkers of response to anti-CTLA-4 or anti-PD-1 therapy. Using a panel of ~ 40 surface and intracellular markers, we performed in-depth phenotypic and functional immune profiling to identify potential predictive biomarker candidates. Results Immune profiling of baseline peripheral blood samples using CyTOF revealed that anti-CTLA-4 and anti-PD-1 therapies have distinct sets of candidate biomarkers. The distribution of CD4+ and CD8+ memory/non-memory cells and other memory subsets was different between responders and non-responders to anti-CTLA-4 therapy. In anti-PD-1 (but not anti-CTLA-4) treated patients, we discovered differences in CD69 and MIP-1β expressing NK cells between responders and non-responders. Finally, multivariate analysis was used to develop a model for the prediction of response. Conclusions Our results indicate that anti-CTLA-4 and anti-PD-1 have distinct predictive biomarker candidates. CD4+ and CD8+ memory T cell subsets play an important role in response to anti-CTLA-4, and are potential biomarker candidates. For anti-PD-1 therapy, NK cell subsets (but not memory T cell subsets) correlated with clinical response to therapy. These functionally active NK cell subsets likely play a critical role in the anti-tumor response triggered by anti-PD-1.http://link.springer.com/article/10.1186/s40425-018-0328-8 |
| spellingShingle | Priyanka B. Subrahmanyam Zhiwan Dong Daniel Gusenleitner Anita Giobbie-Hurder Mariano Severgnini Jun Zhou Michael Manos Lauren M. Eastman Holden T. Maecker F. Stephen Hodi Distinct predictive biomarker candidates for response to anti-CTLA-4 and anti-PD-1 immunotherapy in melanoma patients Journal for ImmunoTherapy of Cancer |
| title | Distinct predictive biomarker candidates for response to anti-CTLA-4 and anti-PD-1 immunotherapy in melanoma patients |
| title_full | Distinct predictive biomarker candidates for response to anti-CTLA-4 and anti-PD-1 immunotherapy in melanoma patients |
| title_fullStr | Distinct predictive biomarker candidates for response to anti-CTLA-4 and anti-PD-1 immunotherapy in melanoma patients |
| title_full_unstemmed | Distinct predictive biomarker candidates for response to anti-CTLA-4 and anti-PD-1 immunotherapy in melanoma patients |
| title_short | Distinct predictive biomarker candidates for response to anti-CTLA-4 and anti-PD-1 immunotherapy in melanoma patients |
| title_sort | distinct predictive biomarker candidates for response to anti ctla 4 and anti pd 1 immunotherapy in melanoma patients |
| url | http://link.springer.com/article/10.1186/s40425-018-0328-8 |
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