General Session II
AB107. SOH21AS190. Timing is everything; manipulating the surgery induced immunosuppressive milieu into a therapeutic target
Noel Edward Donlon1,2, Maria Davern2, Andrew Sheppard2, Michael McClean2, Sinead Ramjit1, Robert Power1, Conall Hayes1, Hugo Temperley1, Ryan Roopnarinesingh1, Jarlath Bolger1, Waqas Butt1, Narayanasamy Ravi1, Claire Donohoe1, Margaret Dunne1, Jacintha OSullivan1, John Reynolds1, Joanne Lysaght1
1Department of Surgery, St. James’s Hospital, Dublin, Ireland; 2Department of Surgery, Trinity Centre for Health Sciences, Trinity College Dublin, St. James’s Hospital, Dublin, Ireland
Background: Immune checkpoint inhibitors (ICIs) are being investigated for their role as an adjunct in the multimodal treatment of oesophageal cancer. The most appropriate time to incorporate ICIs remains unknown. Our study profiles systemic anti-tumour immunity perioperatively to help inform the optimal timing of ICIs into current standards of care for oesophageal adenocarcinoma (OAC) patients.
Methods: Systemic immunity was immunophenotyped pre- and post-oesophagectomy on days 0, 1, 3, 7 and week 6 by flow cytometry (n=14). The frequency of circulating lymphocytes, T cells, cytotoxic and helper T lymphocytes was profiled longitudinally including the proportion of T cell subsets in circulation. This study also profiled immune checkpoint expression on circulating T cells including: PD-1, CTLA-4, TIGIT, TIM-3, LAG-3, PD-L1 and PD-L2. Markers of immunogenicity (calreticulin, HMGB1 and MIC-A/B) were also assessed.
Results: The frequency of naïve T cells increased in circulation from POD-0 to POD-7 (P<0.01) but returned to baseline at week 6. Effector memory T cells decreased by POD7 (P<0.01) returning to normal by week 6. Increases in activated circulating CD27+ T cells was observed from POD-0 to POD-7 (P<0.01), interestingly remaining high in a proportion of patients that experienced complications. The percentage of immune checkpoint positive T cells peaked on POD-1 and was substantially decreased by week 6 (P<0.01).
Conclusions: We observed increased T cell activation and immune checkpoints immediately post-surgery with returns to baseline by week 6. These results suggest that ICIs such as anti-PD-1 may be beneficial immediately post-surgery to maintain T cell activation and prevent exhaustion of this increased population of activated T cells observed immediately post-surgery.
Keywords: Major oncological resection; immunosuppression; immune checkpoints; T cell activation; oesophageal adenocarcinoma
Acknowledgments
Funding: None.
Conflicts of Interest: The authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
doi: 10.21037/map-21-ab107
Cite this abstract as: Donlon NE, Davern M, Sheppard A, McClean M, Ramjit S, Power R, Hayes C, Temperley H, Roopnarinesingh R, Bolger J, Butt W, Ravi N, Donohoe C, Dunne M, OSullivan J, Reynolds J, Lysaght J. SOH21AS190. Timing is everything; manipulating the surgery induced immunosuppressive milieu into a therapeutic target. Mesentery Peritoneum 2021;5:AB107.
