Abstract B060: Clonal composition of αβ and γδ T cells in primary human neuroblastoma tumors – Is every child unique?
Bibliographic record
Abstract
Abstract Alpha beta (ab) T cells are immune cells that play a key role in the adaptive immune system. Over the years many different ab T cell subtypes have been defined including cells with anti-tumor cytotoxic functions. Gamma delta (gd) T cells are considered the bridge between innate and adaptive immunity. While rules of antigen recognition by gd T cells remain poorly understood, this recognition takes place in the absence of classical antigen presentation on MHC molecules. In neuroblastoma (NB), the most common and deadly extracranial tumor in children, different subtypes of T cells have been identified in the tumor microenvironment (TME) and their presence is correlated to improved prognosis. However, it remains unknown whether T cells in the TME have clonally expanded, and if yes, which antigens they recognize. Our aim is thus to uncover the clonal composition of T cells in primary human NB tumors including to elucidate ligand recognition in gd T cells. To address these questions, we performed flow cytometry analysis to elucidate gd T cell composition in 14 patient samples, and additionally performed single-cell (sc) RNA/VDJ-seq experiments to characterize clonal composition and functional states of ab and gd T cells infiltrating NB tumors from 11 patients for which 4 had a matched blood sample. In patients' blood, as expected, most gd T cells detected were Vg9Vd2+ cells. In contrast, the majority of detected infiltrating gd T cells in NB tumors were Vd1+ cells. scRNA/VDJ-seq experiments revealed prominent clonal expansion of both ab and gd T cells varying between patients. Clonal expansion was particularly prominent for gd T cells in one female intermediate risk patient’s tumor where nearly half of the cells represented one of the two top expanded clones with unique Vd1 and Vd3 TCRs. Interestingly, we detected Vd1/ Vd3 expanded clones with both a clear cytotoxic signature and with a possible wound healing phenotype. Taken together, drastic clonal expansion of both ab and gd T cells in NB suggests that these cells may recognize antigens present in the TME providing possibilities for immunotherapy. Citation Format: Bronte Manouk Verhoeven, Kewei Ye, Jakob Stenman, Per Kogner, John Inge Johnsen, Oscar Bedoya Reina, Taras Kreslavskiy, Ninib Baryawno. Clonal composition of αβ and γδ T cells in primary human neuroblastoma tumors – Is every child unique [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr B060.
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 | 0.000 | 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".