VSSP abrogates murine ovarian tumor-associated myeloid cell-driven immune suppression and induces M1 polarization in tumor-associated macrophages from ovarian cancer patients
Abstract The ovarian tumor microenvironment (TME) is characterized by the accumulation of immunosuppressive tumor-associated macrophages (TAMs) and granulocytic cells. Very small size particles (VSSP), comprised of the ganglioside NAcGM3 and Neisseria meningitidis derived outer membra...
| Main Authors: | , , , , , , , , , , , , |
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| Drugi avtorji: | |
| Format: | Article |
| Jezik: | English |
| Izdano: |
Springer Berlin Heidelberg
2022
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| Online dostop: | https://hdl.handle.net/1721.1/145935 |
| _version_ | 1826191588220469248 |
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| author | Khan, ANM N. H. Emmons, Tiffany R. Magner, William J. Alqassim, Emad Singel, Kelly L. Ricciuti, Jason Eng, Kevin H. Odunsi, Kunle Tomasi, Thomas B. Lee, Kelvin Abrams, Scott I. Mesa, Circe Segal, Brahm H. |
| author2 | Koch Institute for Integrative Cancer Research at MIT |
| author_facet | Koch Institute for Integrative Cancer Research at MIT Khan, ANM N. H. Emmons, Tiffany R. Magner, William J. Alqassim, Emad Singel, Kelly L. Ricciuti, Jason Eng, Kevin H. Odunsi, Kunle Tomasi, Thomas B. Lee, Kelvin Abrams, Scott I. Mesa, Circe Segal, Brahm H. |
| author_sort | Khan, ANM N. H. |
| collection | MIT |
| description | Abstract
The ovarian tumor microenvironment (TME) is characterized by the accumulation of immunosuppressive tumor-associated macrophages (TAMs) and granulocytic cells. Very small size particles (VSSP), comprised of the ganglioside NAcGM3 and Neisseria meningitidis derived outer membrane vesicles, is being developed as a nanoparticulated modulator of innate immunity. Prior studies have shown that VSSP enhanced antigen-specific cytotoxic T cell responses and reduced the suppressive phenotype of splenic granulocytic cells in tumor-bearing mice. Here, we hypothesized that intraperitoneal VSSP would modify myeloid cell accumulation and phenotypes in the ovarian TME and abrogate suppressor function of TAMs and tumor-associated granulocytic cells. In the ID8 syngeneic model of epithelial ovarian cancer, VSSP reduced peritoneal TAMs and induced M1-like polarization in TAMs. In addition, VSSP stimulated peritoneal inflammation characterized by increased granulocytes and monocytes, including inflammatory monocytic cells. VSSP treatment resulted in peritoneal TAMs and granulocytic cells being less suppressive of ex vivo stimulated CD8+ T cell responses. VSSP alone and combined with anti-PD-1 modestly but significantly prolonged survival in tumor-bearing mice. In addition, ex vivo treatment with VSSP induced M1-like polarization in TAMs from patients with metastatic ovarian cancer and variably abrogated their suppressor phenotype. VSSP treatment also partially abrogated the induction of suppressor function in healthy donor neutrophils exposed to ascites supernatants from patients with ovarian cancer. Together, these results point to VSSP reprogramming myeloid responses resulting in abrogation of suppressive pathways and raise the potential for administration of VSSP into the TME to enhance anti-tumor immunity. |
| first_indexed | 2024-09-23T08:58:34Z |
| format | Article |
| id | mit-1721.1/145935 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T08:58:34Z |
| publishDate | 2022 |
| publisher | Springer Berlin Heidelberg |
| record_format | dspace |
| spelling | mit-1721.1/1459352023-03-09T05:11:26Z VSSP abrogates murine ovarian tumor-associated myeloid cell-driven immune suppression and induces M1 polarization in tumor-associated macrophages from ovarian cancer patients Khan, ANM N. H. Emmons, Tiffany R. Magner, William J. Alqassim, Emad Singel, Kelly L. Ricciuti, Jason Eng, Kevin H. Odunsi, Kunle Tomasi, Thomas B. Lee, Kelvin Abrams, Scott I. Mesa, Circe Segal, Brahm H. Koch Institute for Integrative Cancer Research at MIT Abstract The ovarian tumor microenvironment (TME) is characterized by the accumulation of immunosuppressive tumor-associated macrophages (TAMs) and granulocytic cells. Very small size particles (VSSP), comprised of the ganglioside NAcGM3 and Neisseria meningitidis derived outer membrane vesicles, is being developed as a nanoparticulated modulator of innate immunity. Prior studies have shown that VSSP enhanced antigen-specific cytotoxic T cell responses and reduced the suppressive phenotype of splenic granulocytic cells in tumor-bearing mice. Here, we hypothesized that intraperitoneal VSSP would modify myeloid cell accumulation and phenotypes in the ovarian TME and abrogate suppressor function of TAMs and tumor-associated granulocytic cells. In the ID8 syngeneic model of epithelial ovarian cancer, VSSP reduced peritoneal TAMs and induced M1-like polarization in TAMs. In addition, VSSP stimulated peritoneal inflammation characterized by increased granulocytes and monocytes, including inflammatory monocytic cells. VSSP treatment resulted in peritoneal TAMs and granulocytic cells being less suppressive of ex vivo stimulated CD8+ T cell responses. VSSP alone and combined with anti-PD-1 modestly but significantly prolonged survival in tumor-bearing mice. In addition, ex vivo treatment with VSSP induced M1-like polarization in TAMs from patients with metastatic ovarian cancer and variably abrogated their suppressor phenotype. VSSP treatment also partially abrogated the induction of suppressor function in healthy donor neutrophils exposed to ascites supernatants from patients with ovarian cancer. Together, these results point to VSSP reprogramming myeloid responses resulting in abrogation of suppressive pathways and raise the potential for administration of VSSP into the TME to enhance anti-tumor immunity. 2022-10-24T12:10:51Z 2022-10-24T12:10:51Z 2022-02-15 2022-10-24T03:15:45Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/145935 Khan, ANM N. H., Emmons, Tiffany R., Magner, William J., Alqassim, Emad, Singel, Kelly L. et al. 2022. "VSSP abrogates murine ovarian tumor-associated myeloid cell-driven immune suppression and induces M1 polarization in tumor-associated macrophages from ovarian cancer patients." en https://doi.org/10.1007/s00262-022-03156-x Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature application/pdf Springer Berlin Heidelberg Springer Berlin Heidelberg |
| spellingShingle | Khan, ANM N. H. Emmons, Tiffany R. Magner, William J. Alqassim, Emad Singel, Kelly L. Ricciuti, Jason Eng, Kevin H. Odunsi, Kunle Tomasi, Thomas B. Lee, Kelvin Abrams, Scott I. Mesa, Circe Segal, Brahm H. VSSP abrogates murine ovarian tumor-associated myeloid cell-driven immune suppression and induces M1 polarization in tumor-associated macrophages from ovarian cancer patients |
| title | VSSP abrogates murine ovarian tumor-associated myeloid cell-driven immune suppression and induces M1 polarization in tumor-associated macrophages from ovarian cancer patients |
| title_full | VSSP abrogates murine ovarian tumor-associated myeloid cell-driven immune suppression and induces M1 polarization in tumor-associated macrophages from ovarian cancer patients |
| title_fullStr | VSSP abrogates murine ovarian tumor-associated myeloid cell-driven immune suppression and induces M1 polarization in tumor-associated macrophages from ovarian cancer patients |
| title_full_unstemmed | VSSP abrogates murine ovarian tumor-associated myeloid cell-driven immune suppression and induces M1 polarization in tumor-associated macrophages from ovarian cancer patients |
| title_short | VSSP abrogates murine ovarian tumor-associated myeloid cell-driven immune suppression and induces M1 polarization in tumor-associated macrophages from ovarian cancer patients |
| title_sort | vssp abrogates murine ovarian tumor associated myeloid cell driven immune suppression and induces m1 polarization in tumor associated macrophages from ovarian cancer patients |
| url | https://hdl.handle.net/1721.1/145935 |
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