Cooperation between chemotherapy and immune checkpoint blockade to enhance anti-tumour T cell immunity in oesophageal adenocarcinoma

• DOI: 10.1016/j.tranon.2022.101406
• Publication Date: 2022-03-30T22:07:07Z
• Authors: Maria Davern; Noel E. Donlon; Fiona O’ Connell; Andrew D. Sheppard; Conall Hayes; Ross King; Hugo Temperley; Christine Butler; Anshul Bhardwaj; Jenny Moore; Dara Bracken-Clarke; Claire Donohoe; Narayanasamy Ravi; John V. Reynolds; Stephen G. Maher; Melissa J. Conroy; Joanne Lysaght
• Keywords: Immune checkpoint

Response rates to immune checkpoint blockade (ICB) remain low in oesophageal adenocarcinoma (OAC). Combining ICB with immunostimulatory chemotherapies boost response is an attractive approach for converting 'cold' tumours into 'hot' tumours. This study profiled (IC) expression on circulating and tumour-infiltrating T cells OAC patients correlated these findings clinical characteristics. The effect of first-line chemotherapy regimens (FLOT CROSS) anti-tumour cell immunity was assessed help guide design combinations the setting. ability enhance lymphocyte-mediated cytolysis absence presence post-FLOT post-CROSS tumour secretome by a CCK-8 assay. Expression ICs positively higher grade subsequent poor neoadjuvant treatment. First-line substantially altered IC profiles increasing PD-1, A2aR, KLRG-1, PD-L1, PD-L2 CD160 decreasing TIM-3 LAG-3. In addition, pro-inflammatory cytokine were enhanced regimens. activation status significantly altered; both upregulated co-stimulatory markers ICOS CD69 yet downregulated marker CD27. However, attenuated chemotherapy-induced downregulation CD27 promoted differentiation effector memory terminally differentiated state. Importantly, dual nivolumab-ipilimumab treatment increased cells, further secretome. These justify rationale administer ICBs concurrently chemotherapies.