Acidosis significantly alters immune checkpoint expression profiles of T cells from oesophageal adenocarcinoma patients

• DOI: 10.1007/s00262-022-03228-y
• Publication Date: 2022-06-16T14:03:06Z
• Authors: Maria Davern; Noel E. Donlon; Fiona O’Connell; Caoimhe Gaughan; Cillian O’Donovan; Mohammed Habash; Andrew D. Sheppard; Michael MacLean; Margaret R. Dunne; Jenny Moore; Hugo Temperley; Melissa J. Conroy; Christine Butler; Anshul Bhardwaj; Narayanasamy Ravi; Claire L. Donohoe; John V. Reynolds; Joanne Lysaght
• Keywords: Immune checkpoint

Tumour acidosis contributes to cancer progression by inhibiting anti-tumour immunity. However, the effect of on T cell phenotypes in oesophageal adenocarcinoma (OAC) is unknown. Therefore, this study investigated profiles and if immune checkpoint blockade (ICB) could enhance immunity under acidosis. Acidic conditions substantially altered expression OAC patient-derived cells, upregulating TIM-3, LAG-3 CTLA-4. Severe (pH 5.5) significantly decreased percentage central memory CD4+ an that was attenuated ICB treatment. increased production IFN-γ moderate 6.6) but not severe IL-10 cells acidic only. A link between lactate metastasis also depicted; patients with nodal had higher serum levels (p = 0.07) which positively correlated circulating pro-angiogenic factor Tie-2. Our findings establish acidosis-induced upregulation checkpoints may potentially contribute evasion disease OAC. curtailed efficacy, supporting a rationale for utilizing systemic oral buffers neutralize tumour acidity improve efficacy. Study schematic-PBMCs were isolated from (A) expanded ex vivo 7 days using anti-CD3/28 +IL-2 activation protocol (B) further cultured 48 h increasing absence or presence (nivolumab, ipilimumab dual nivolumab + ipilimumab) (C). Immunophenotyping then carried out assess (D). Serum assessed (E-F) patient demographics (G) immune/pro-angiogenic cytokines determined multiplex ELISA (H). Key Findings-severe upregulated multiple (I). Efficacy (J). Circulating tie-2 found who (K).