Abstract A108: Distinct immune suppressive myeloid cell populations are induced by hypoxic mammary tumors and differentially promote metastatic tumor growth
Bibliographic record
Abstract
Abstract Some primary tumors induce the accumulation of myeloid cells in distant tissues, and a role for these cells in promoting metastasis is emerging. However, the identity and function of these myeloid cells in metastatic breast cancer is unclear. Using transplantable and spontaneous metastatic mammary tumor models, we have found that immune suppressive CD11b+Gr1+ myeloid-derived suppressor cells (MDSCs) and CD11b+F4/80+Gr1- macrophages (MΦs) accumulate in the spleens and lungs of tumor-bearing mice due to proteins secreted by poorly oxygenated (hypoxic) cells in primary tumors. We also found that immunosuppressive MDSCs remain elevated in the lungs for several weeks after surgical resection of the primary tumor, and that these MDSCs profoundly enhance subsequent pulmonary metastatic growth. To decrease MDSC levels in tissues, we therapeutically targeted hypoxic tumor cells or used all-trans retinoic acid (ATRA) to differentiate immature MDSCs into mature MΦs. Targeting hypoxic tumor cells or ATRA treatment both decreased MDSC levels in tissues, although ATRA-treated mice had more MΦs and significantly more lung metastases than untreated mice. Consistent with these data, we found that MΦs were 30-fold more potent suppressors of T cell-mediated immune responses than MDSCs on a per cell basis, and that MΦs and MDSCs suppress via different reactive oxygen species (ROS)-mediated mechanisms. Taken together, these data suggest that hypoxia-mediated accumulation of MDSCs in the lungs can have long-lasting implications for the growth of secondary metastatic tumors after treatment. However, due to the immune suppressive function of MΦs, our data caution against inducing the terminal differentiation of MDSCs into MΦs for breast cancer treatment. These studies support the development of therapies to enhance anti-tumor immunity by targeting hypoxic tumor cells, MDSCs, and MΦs for the treatment of metastatic breast cancer. Citation Format: Melisa J. Hamilton, Momir Bosiljcic, Nancy E. LePard, Bryant T. Harbourne, Gerald Krystal, Kevin L. Bennewith. Distinct immune suppressive myeloid cell populations are induced by hypoxic mammary tumors and differentially promote metastatic tumor growth. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research: Genetics, Biology, and Clinical Applications; Oct 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2013;11(10 Suppl):Abstract nr A108.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".