Abstract A68: Phosphodiesterase-5 inhibition modulates surgery-induced myeloid-derived suppressor cells to reduce postoperative metastatic disease
Bibliographic record
Abstract
Abstract Purpose: Cancer surgery while necessary for primary tumor removal, has been shown to induce immune suppression and promote metastases in preclinical models and human cancer surgery patients. Activating the immune system and reversing immunosuppression have emerged as promising ways to treat cancer and they can be safely employed in the perioperative period. In this study, we evaluated the immunotherapeutic potential of phosphodiesterase-5 (PDE-5) inhibitors to target surgery-induced myeloid-derived suppressor cells (MDSC) and restore natural killer (NK) cell function in the clinically relevant perioperative period. Experimental Design: Immunocompetent mice tumor models of major surgery were used to characterize the functional suppression of surgery-induced MDSC and to assess the in vivo efficacy of perioperative PDE5 inhibition. In cancer surgery patients with abdominal malignancies, we assessed NK cell function following co-culture with MDSC and PDE5 inhibition. Results: Perioperative PDE5 inhibition reverses surgery-induced immunosuppression. In particular, sildenafil reduces surgery-derived granulocytic-MDSC (gMDSC) function through downregulation of arginase 1 (ARG1), IL4Rα; and reactive oxygen species (ROS) expression, enabling NK cell antitumor cytotoxicity and reducing postoperative disease recurrence. By removing surgery-derived immunosuppressive mechanisms on MDSC, sildenafil synergizes with the administration of perioperative influenza vaccination to reduce postoperative metastasis. Importantly, sildenafil reverses MDSC suppression in cancer surgery patients. Conclusions: These findings demonstrate that PDE5 inhibitors reduce postoperative metastasis by their ability to inhibit surgery-induced MDSC. Further clinical studies are warranted to investigate the immunotherapeutic role of PDE5 inhibitors in combination with cancer surgery. Note: This abstract was not presented at the conference. Citation Format: Lee-Hwa Tai, Almohanad A. Alkayyal, Katherine E. Baxter, Leonard Angka, Mike Kennedy, Christiano Tanese de Souza, Rebecca C. Auer. Phosphodiesterase-5 inhibition modulates surgery-induced myeloid-derived suppressor cells to reduce postoperative metastatic disease. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr A68.
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 | 0.001 |
| 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".