Abstract 249: Assessment of PD-L1 expression and tumor-associated lymphocytes in pediatric cancer tissues
Bibliographic record
Abstract
Abstract PD-1 signaling in the tumor microenvironment dampens immune responses to cancer and blocking this axis induces anti-tumor effects in several malignancies. Some studies have demonstrated increased efficacy of PD-1 blockade when tumor cells express PD-L1. Clinical studies of PD-1 blockade have not yet been conducted in pediatric patients and little is known regarding PD-L1 expression in common childhood cancers. We characterized PD-L1 expression and Tumor Associated Immune Cells (TAIC, lymphocytes and macrophages) in common pediatric cancers. Whole slide sections (n = 91) and tissue microarrays (n = 365) were evaluated by IHC for PD-L1 expression using the 28-8 anti-PD-L1 mAb in an automated Dako assay. PD-L1 expression was considered positive when at least 1% of tumor cells analyzed demonstrated plasma membrane staining. TAIC were also assessed for expression of PD-L1, and a subset of 60 tumors were assessed for CD3, CD4, CD8, CD45RO, PD-1, and FoxP3 expression on TAIC. Nine percent (N = 40) of evaluable tumors expressed PD-L1. Highest frequency histotypes comprised non-Hodgkin lymphoma (80%, 8/10), glioblastoma multiforme (30%, 6/20), and neuroblastoma (14%, 17/118). No PD-L1 staining was observed in Ewing sarcoma (0/20) or medulloblastoma (0/40). Despite a relatively low frequency of PD-L1+ pediatric cancers, the majority contained TAIC (73%, 334/456). Of these TAIC+ tumors, 73% of samples contained lymphocytes only, 25% contained lymphocytes and macrophages and 3% contained macrophages only. Twenty-one percent of TAIC+ samples demonstrated PD-L1 expression on TAIC, mostly comprising PD-L1 expression on macrophages (65%, 60/92), while lymphocytes expressed PD-L1 in only 7% (22/324). Taken together, PD-L1 was expressed in tumor and/or TAIC in 20% (90/456). Sixty samples were further analyzed to characterize TAIC, with 77% of the samples demonstrating infiltration of CD8+ T cells, most of which expressed CD45RO. Fox-P3 and PD-1 were expressed in 42% and 47% of the samples respectively. In summary, this provides the most comprehensive analysis of PD-L1 expression in pediatric associated cancer to date. Results show that a subset of pediatric cancers demonstrate tumor associated PD-L1 expression, while a much larger fraction demonstrate infiltration with tumor associated lymphocytes. Further preclinical and clinical investigation will define the predictive nature of PD-L1 expression in childhood cancers, but available data is not sufficient to exclude enrollment to clinical trials based on PD-L1 status. Citation Format: Robbie G. Majzner, Jason S. Simon, Joseph F. Grosso, Daniel Martinez, Bruce Pawel, Mariarita Santi-Vincini, Melinda S. Merchant, Poul Sorensen, Crystal L. Mackall, John M. Maris. Assessment of PD-L1 expression and tumor-associated lymphocytes in pediatric cancer tissues. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 249. doi:10.1158/1538-7445.AM2015-249
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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 | 0.001 | 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) | 0.003 | 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".