Article ; Online: Allogeneic NK cells induce monocyte-to-dendritic cell conversion, control tumor growth, and trigger a pro-inflammatory shift in patient-derived cultures of primary and metastatic colorectal cancer.
Journal for immunotherapy of cancer
2023 Volume 11, Issue 12
Abstract: Introduction: Natural killer (NK) cells are innate lymphocytes with a key role in the defense against tumors. Recently, allogeneic NK cell-based therapies have gained interest because of their ability to directly lyse tumor cells without inducing graft- ... ...
| Abstract | Introduction: Natural killer (NK) cells are innate lymphocytes with a key role in the defense against tumors. Recently, allogeneic NK cell-based therapies have gained interest because of their ability to directly lyse tumor cells without inducing graft-versus-host disease. As NK cells are also able to influence the function of other immune cells (most notably dendritic cells (DC)), a better understanding of the effects of allogeneic NK cell products on the host immune system is required. In this study, we analyzed the effects of an allogeneic off-the-shelf NK cell product, on the tumor microenvironment (TME) of primary and metastatic colorectal cancer (pCRC and mCRC, respectively). Moreover, we explored if the combination of NK cells with R848, a toll-like receptors 7/8 ligand, could further enhance any pro-inflammatory effects. Methods: Ex vivo expanded umbilical cord blood stem cell derived NK cells were co-cultured with pCRC or mCRC single-cell suspensions in the presence or absence of R848 for 5 days, during and after which flow cytometry and cytokine release profiling were performed. Results: NK cells efficiently induced lysis of tumor cells in both pCRC and mCRC single-cell suspensions and thereby controlled growth rates during culture. They also induced differentiation of infiltrating monocytic cells to an activated DC phenotype. Importantly, this NK-mediated myeloid conversion was also apparent in cultures after tumor cell depletion and was further enhanced by combining NK cells with R848. Moreover, NK cells, and to a greater extent, the combination of NK cells and R848, triggered CD8 Conclusion: Allogeneic NK cells engaged in favorable myeloid crosstalk, displayed effective antitumor activity and, when combined with R848, induced a pro-inflammatory shift of the CRC TME. These findings prompt the investigation of NK cells and R848 as a combination therapy for solid tumors. |
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| MeSH term(s) | Humans ; Monocytes ; Dendritic Cells ; Killer Cells, Natural ; Interleukin-12/pharmacology ; Colorectal Neoplasms/therapy ; Hematopoietic Stem Cell Transplantation ; Tumor Microenvironment |
| Chemical Substances | Interleukin-12 (187348-17-0) |
| Language | English |
| Publishing date | 2023-12-06 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2719863-7 |
| ISSN | 2051-1426 ; 2051-1426 |
| ISSN (online) | 2051-1426 |
| ISSN | 2051-1426 |
| DOI | 10.1136/jitc-2023-007554 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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