Abstract P3-05-12: VISTA expression on tumor-infiltrating lymphocytes in breast cancer: Clinical correlates and association with PD-1
Bibliographic record
Abstract
Abstract Background: The V-domain containing Ig Suppressor of T Cell Activation (VISTA) is a recently discovered immune checkpoint receptor with homology to PD-1. VISTA expression on tumor-infiltrating lymphocytes (TILs) blocks their proliferation and effector functions. Recent pre-clinical data in cancer mouse models treated with anti-VISTA and anti-PD-L1 combinations showed promising results and non-redundant functions of VISTA and PD-L1 blockade. However, the expression and prognostic value of VISTA+ TILs in primary breast tumors has not been investigated in detail. Here we assess expression, prognostic value, and associations of VISTA+TILs with other immune checkpoint markers (PD-1/PD-L1, LAG-3, and IDO-1) and with H&E TIL counts. Methods: A tissue microarray consisting of breast carcinoma primary excision specimens (n=330) from the University of British Columbia hospital, linked to detailed clinicopathological data and outcomes, was used in this study. Patients from this cohort did not receive neoadjuvant treatment. A VISTA antibody (Clone D1L2G) was applied on a 4μm section of the tissue microarray by immunohistochemistry using a Ventana automated stainer. VISTA+TILs in direct contact with tumor nest were scored and reported as absolute count per 0.6mm core. Positive cases were defined as cases with VISTA+TILs≥1. All descriptive and survival analyses were conducted using SPSS software. Results: VISTA+TILs were present in 30% of cases and were significantly (p<0.05) associated with younger age (<50 years old), larger tumors (>2cm), hormone receptor negativity (ER/PR) and high Ki67proliferation index (≥13.25%). Almost half (48%) of basal-like breast cancers were positive for VISTA expressing TILs. No significant prognostic associations were observed in this cohort. Among the immune checkpoint receptors analyzed, VISTA+TILs were highly associated with PD-1+ TILs: 79% of cases positive for PD-1+TILs were also infiltrated by VISTA+TILs. Interestingly, we found that VISTA+TILs and PD-1+TILs were enriched in cases with otherwise low levels (<10%) of H&E TILs. Conclusions: Our study identifies the presence of VISTA+TILs in breast cancer patients and its strong association with PD-1+TILs. These results suggest that VISTA blockade could be a good candidate for combination therapy with other immune checkpoint inhibitors, a concept being tested in early phase clinical trials. Validation of these findings in a larger independent cohort powered for multivariate analysis is currently ongoing. Citation Format: Burugu S, Gao D, Nielsen TO. VISTA expression on tumor-infiltrating lymphocytes in breast cancer: Clinical correlates and association with PD-1 [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-05-12.
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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 | 0.000 | 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) | 0.004 | 0.001 |
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".