A Complex Interplay of Tumor Microenvironment Could Enhance Cholangiocarcinoma Progression Even After Surgery: A Prospective Study
Bibliographic record
Abstract
Background: The current study was conducted to explore the impact of macrophages and programmed cell death protein 1 (PD-1) expression on tumor-infiltrating lymphocytes (TILs) on treatment outcomes and to define the interaction between these factors and the clinicopathologic features of advanced cholangiocarcinoma (CCA) patients. Methods: Twenty-five patients with metastatic CCA were recruited for the current study from El-Rajhi Hospital and the Clinical Oncology Department of Assiut University. Additionally, 19 healthy controls were included. Before the flow cytometric detection of immune cells, the diagnosis and staging of CCA were performed based on surgical intervention, imaging, carbohydrate antigen 19-9 (CA19-9), and carcinoembryonic antigen (CEA) determinations. This was followed by flow cytometric detection of CD4+, CD8+, CD4+PD-1+, CD8+PD-1+, and CD11b+CD68+ macrophages in the peripheral blood of both patients and controls. Results: The current results revealed higher levels of CD4+, CD8+, and CD11b+CD68+ macrophages in controls compared to patients. At the same time, PD-1 expression was significantly higher in patients compared to controls. CD4+ was correlated with improved progression-free survival (PFS), while CD8+PD-1 was associated with shorter PFS. In general, CD4+ and CD8+ levels progressively increased with improved response to treatments, differentiation, single organ site metastasis, and surgical interventions. On the contrary, PD-1 expression and macrophages progressively increased with worsening response, dedifferentiation, multiple organ sites, and surgical interventions. The median PFS was 12 months, and the mean ± standard error (SE) was 13.1 ± 1.3. Conclusions: CCA has a desmoplastic microenvironment with complex immunologic topography and tumor-reactive stroma. The immune landscape of the peripheral blood mononuclear cells (PBMCs) in CCA patients before treatment could reflect the state of systemic immune function and response to treatments. Our results revealed that T-lymphocytes correlated with better prognosis while macrophages and PD-1+ expression were associated with poor outcomes.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".