Other
12 Authors
- Egeblad M,
- Liu B,
- Almeida AS,
- Adams S,
- McNeish IA,
- He XY,
- Spector DL,
- Sun L,
- Han X,
- Kees T,
- Ng D,
- Gimotty P
| First Author | Sun L | Year | 2021 |
| Journal | Cancer Cell | Volume | 39 |
| Issue | 10 | Pages | 1361-1374.e9 |
| PubMed ID | 34478639 | Mgi Jnum | J:353197 |
| Mgi Id | MGI:6780638 | Doi | 10.1016/j.ccell.2021.08.005 |
| Citation | Sun L, et al. (2021) Activating a collaborative innate-adaptive immune response to control metastasis. Cancer Cell 39(10):1361-1374.e9 |
| abstractText | Tumor-associated macrophages (TAMs) promote metastasis and inhibit T cells, but macrophages can be polarized to kill cancer cells. Macrophage polarization could thus be a strategy for controlling cancer. We show that macrophages from metastatic pleural effusions of breast cancer patients can be polarized to kill cancer cells with monophosphoryl lipid A (MPLA) and interferon (IFN) gamma. MPLA + IFNgamma injected intratumorally or intraperitoneally reduces primary tumor growth and metastasis in breast cancer mouse models, suppresses metastasis, and enhances chemotherapy response in an ovarian cancer model. Both macrophages and T cells are critical for the treatment's anti-metastatic effects. MPLA + IFNgamma stimulates type I IFN signaling, reprograms CD206(+) TAMs to inducible NO synthase (iNOS)(+) macrophages, and activates cytotoxic T cells through macrophage-secreted interleukin-12 (IL-12) and tumor necrosis factor alpha (TNFalpha). MPLA and IFNgamma are used individually in clinical practice and together represent a previously unexplored approach for engaging a systemic anti-tumor immune response. |
