Characterization of host immune cell infiltrate in human CAR T cell-mediated xenogeneic graft versus host disease in NSG mice
Bibliographic record
Abstract
Chimeric antigen receptor (CAR) T cells are revolutionary cancer therapies that are Food and Drug Administration-approved for hematologic malignancies and under investigation for solid tumors. The use of allogeneic over autologous CAR T cells offers advantages, including broader availability and reduced costs. However, allogeneic CAR T cells frequently trigger graft versus host disease (GvHD), a complication observed in patients and experimental models where human CAR T cells are delivered into immunocompromised mice. To understand the contribution of the mouse immune response to human CAR T cell-mediated xenogeneic GvHD, we analyzed GvHD lesions in a human xenograft tumor model in NOD.Cg- Prkdc scid Il2rg tm1Wjl /SzJ (NSG) mice. The animals were treated with second-generation CAR T cells targeting a human tumor-specific antigen without a murine homolog. Mice treated with CAR T cells had more severe GvHD lesions than control mice receiving nontransduced (NT) T cells. Also, tumor burden was negatively correlated with GvHD lesion severity. Immunohistochemical characterization of the GvHD lesions showed that approximately 45% of the immune cell infiltrate consisted of murine cells, most of which were IBA1+ histiocytes, with a small population of CD11c+ dendritic cells. The murine histiocytes expressed activation/antigen presentation markers, including high levels of the costimulatory molecule CD86. Analysis of macrophage polarization indicated an M2-like phenotype. These findings demonstrate a significant contribution of the mouse histiocytic compartment to lesions of human CAR T cell-mediated xenogeneic GvHD. Our results suggest that CD86+ murine antigen-presenting cells help trigger and sustain the xenoreactive CAR T cell response. Furthermore, xenogeneic GvHD exhibits a shift toward M2 polarization in murine macrophages.
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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 | 0.001 | 0.001 |
| 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) | 0.000 | 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".