CD16 and Siglec expression refine the phenotypic heterogeneity of steady-state myeloid-derived suppressor cells
Bibliographic record
Abstract
Background Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) mediate cancer immune suppression by promoting an immunosuppressive microenvironment that inhibits effective anti-tumor immunity. However, they are still a poorly understood, heterogeneous mix of neutrophil subsets. This study aims to determine the Siglec expression profile on several neutrophil subsets and assess their immunosuppressive ability. Methods We identified CD16 high and CD16 low neutrophil subsets from the low-density fractions of human peripheral blood and compared them to high-density neutrophils. We profiled the expression of the entire family of Siglecs on these three key neutrophil populations under steady-state conditions in healthy subjects as well as cancer patients. Moreover, the ability of these populations, isolated from healthy subjects, to suppress T cell proliferation was assessed. Results Two distinct subpopulations were investigated within the low-density fraction of human peripheral blood (CD15 + CD66b + CD16 low and CD15 + CD66b + CD16 high ) and compared to high-density neutrophils (CD15 + CD66b + CD16 high ). We found that in addition to CD33 (Siglec-3), Siglec-5/-14, -7, and -9, are differentially expressed on the CD16 low and CD16 high low-density subsets in both healthy, steady-state subjects, and cancer patients. Upregulated expression of CD33 on the CD16 low cells led to the initial speculation that they are MDSCs. As the differential expression of Siglec-9 between these two populations was striking, we used CD16 and Siglec-9 double staining to quantify these populations, which demonstrated that the CD16 low Siglec-9 low population is greatly upregulated in cancer patients. The CD16 high low-density and high-density neutrophils, but not the CD16 low low-density neutrophils from healthy subjects, inhibited T cell proliferation, indicating that the CD16 low Siglec-9 low population are not MDSCs. Conclusions These results demonstrate that Siglecs are differentially expressed on neutrophil subsets, and along with CD16, may be used to help further define what is a PMN-MDSC. Consistent with current observations by others, PMN-MDSCs may encompass an array of neutrophil subtypes, including low-density neutrophils, and point to the need for more work to precisely define the genetic signatures of PMN-MDSCs.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".