Cancer-specific innate and adaptive immune rewiring drives resistance to PD-1 blockade in classic Hodgkin lymphoma
Abstract Hodgkin Reed-Sternberg (HRS) cells of classic Hodgkin lymphoma (cHL), like many solid tumors, elicit ineffective immune responses. However, patients with cHL are highly responsive to PD-1 blockade, which largely depends on HRS cell-specific retention of MHC class II and implicates CD4+ T ce...
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Nature Portfolio
2024-12-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54512-7 |
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| author | Julia Paczkowska Ming Tang Kyle T. Wright Li Song Kelsey Luu Vignesh Shanmugam Emma L. Welsh Jason L. Weirather Naomi Besson Harrison Olszewski Billie A. Porter Kathleen L. Pfaff Robert A. Redd Fathima Zumla Cader Elisa Mandato Jing Ouyang Eleonora Calabretta Gali Bai Lee N. Lawton Philippe Armand Scott J. Rodig Xiaole Shirley Liu Margaret A. Shipp |
| author_facet | Julia Paczkowska Ming Tang Kyle T. Wright Li Song Kelsey Luu Vignesh Shanmugam Emma L. Welsh Jason L. Weirather Naomi Besson Harrison Olszewski Billie A. Porter Kathleen L. Pfaff Robert A. Redd Fathima Zumla Cader Elisa Mandato Jing Ouyang Eleonora Calabretta Gali Bai Lee N. Lawton Philippe Armand Scott J. Rodig Xiaole Shirley Liu Margaret A. Shipp |
| author_sort | Julia Paczkowska |
| collection | DOAJ |
| description | Abstract Hodgkin Reed-Sternberg (HRS) cells of classic Hodgkin lymphoma (cHL), like many solid tumors, elicit ineffective immune responses. However, patients with cHL are highly responsive to PD-1 blockade, which largely depends on HRS cell-specific retention of MHC class II and implicates CD4+ T cells and additional MHC class I-independent immune effectors. Here, we utilize single-cell RNA sequencing and spatial analysis to define shared circulating and microenvironmental features of the immune response to PD-1 blockade in cHL. Compared with non-responders, responding patients have more circulating CD4+ naïve and central memory T cells and B cells, as well as more diverse CD4+ T cell and B cell receptor repertoires. Importantly, a population of circulating and tumor-infiltrating IL1β+ monocytes/macrophages is detectable in patients with cHL but not healthy donors, and a proinflammatory, tumor-promoting signature of these circulating IL1β+ monocytes is associated with resistance to PD-1 blockade in cHL. Altogether, our findings reveal extensive immune rewiring and complementary roles of CD4+ T cells, B cells and IL1β+ monocytes in the response to PD-1 blockade and suggest that these features can be captured with a peripheral blood test. |
| format | Article |
| id | doaj-art-242a72aa6079470faa09fc9e08004205 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-242a72aa6079470faa09fc9e080042052025-01-05T12:34:34ZengNature PortfolioNature Communications2041-17232024-12-0115111810.1038/s41467-024-54512-7Cancer-specific innate and adaptive immune rewiring drives resistance to PD-1 blockade in classic Hodgkin lymphomaJulia Paczkowska0Ming Tang1Kyle T. Wright2Li Song3Kelsey Luu4Vignesh Shanmugam5Emma L. Welsh6Jason L. Weirather7Naomi Besson8Harrison Olszewski9Billie A. Porter10Kathleen L. Pfaff11Robert A. Redd12Fathima Zumla Cader13Elisa Mandato14Jing Ouyang15Eleonora Calabretta16Gali Bai17Lee N. Lawton18Philippe Armand19Scott J. Rodig20Xiaole Shirley Liu21Margaret A. Shipp22Department of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Data Science, Dana-Farber Cancer InstituteDepartment of Pathology, Brigham and Women’s HospitalDepartment of Data Science, Dana-Farber Cancer InstituteDepartment of Data Science, Dana-Farber Cancer InstituteDepartment of Pathology, Brigham and Women’s HospitalDepartment of Pathology, Brigham and Women’s HospitalDepartment of Data Science, Dana-Farber Cancer InstituteDepartment of Pathology, Brigham and Women’s HospitalDepartment of Pathology, Brigham and Women’s HospitalDepartment of Pathology, Brigham and Women’s HospitalDepartment of Pathology, Brigham and Women’s HospitalDepartment of Data Science, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Data Science, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Pathology, Brigham and Women’s HospitalDepartment of Data Science, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteAbstract Hodgkin Reed-Sternberg (HRS) cells of classic Hodgkin lymphoma (cHL), like many solid tumors, elicit ineffective immune responses. However, patients with cHL are highly responsive to PD-1 blockade, which largely depends on HRS cell-specific retention of MHC class II and implicates CD4+ T cells and additional MHC class I-independent immune effectors. Here, we utilize single-cell RNA sequencing and spatial analysis to define shared circulating and microenvironmental features of the immune response to PD-1 blockade in cHL. Compared with non-responders, responding patients have more circulating CD4+ naïve and central memory T cells and B cells, as well as more diverse CD4+ T cell and B cell receptor repertoires. Importantly, a population of circulating and tumor-infiltrating IL1β+ monocytes/macrophages is detectable in patients with cHL but not healthy donors, and a proinflammatory, tumor-promoting signature of these circulating IL1β+ monocytes is associated with resistance to PD-1 blockade in cHL. Altogether, our findings reveal extensive immune rewiring and complementary roles of CD4+ T cells, B cells and IL1β+ monocytes in the response to PD-1 blockade and suggest that these features can be captured with a peripheral blood test.https://doi.org/10.1038/s41467-024-54512-7 |
| spellingShingle | Julia Paczkowska Ming Tang Kyle T. Wright Li Song Kelsey Luu Vignesh Shanmugam Emma L. Welsh Jason L. Weirather Naomi Besson Harrison Olszewski Billie A. Porter Kathleen L. Pfaff Robert A. Redd Fathima Zumla Cader Elisa Mandato Jing Ouyang Eleonora Calabretta Gali Bai Lee N. Lawton Philippe Armand Scott J. Rodig Xiaole Shirley Liu Margaret A. Shipp Cancer-specific innate and adaptive immune rewiring drives resistance to PD-1 blockade in classic Hodgkin lymphoma Nature Communications |
| title | Cancer-specific innate and adaptive immune rewiring drives resistance to PD-1 blockade in classic Hodgkin lymphoma |
| title_full | Cancer-specific innate and adaptive immune rewiring drives resistance to PD-1 blockade in classic Hodgkin lymphoma |
| title_fullStr | Cancer-specific innate and adaptive immune rewiring drives resistance to PD-1 blockade in classic Hodgkin lymphoma |
| title_full_unstemmed | Cancer-specific innate and adaptive immune rewiring drives resistance to PD-1 blockade in classic Hodgkin lymphoma |
| title_short | Cancer-specific innate and adaptive immune rewiring drives resistance to PD-1 blockade in classic Hodgkin lymphoma |
| title_sort | cancer specific innate and adaptive immune rewiring drives resistance to pd 1 blockade in classic hodgkin lymphoma |
| url | https://doi.org/10.1038/s41467-024-54512-7 |
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