TY - JOUR
T1 - High CD8+ tumour-infiltrating lymphocyte density associates with unfavourable prognosis in oesophageal adenocarcinoma following poor response to neoadjuvant chemoradiotherapy
AU - Koemans, Willem J.
AU - van Dieren, Jolanda M.
AU - van den Berg, Jose G.
AU - Meijer, Gerrit A.
AU - Snaebjornsson, Petur
AU - Chalabi, Myriam
AU - Lecot, Frederig
AU - Riedl, Robert
AU - Krijgsman, Oscar
AU - Hofland, Ingrid
AU - Broeks, Annegien
AU - Voncken, Francine E.M.
AU - Peppelenbosch, Maikel P.
AU - Sosef, Meindert N.
AU - van Sandick, Johanna W.
AU - Kodach, Liudmila L.
N1 - Funding Information:
No funding was received from external parties. We would like to acknowledge the NKI-AVL Core Facility Molecular Pathology and Biobanking (CFMPB) for supplying NKI-AVL Biobank material and laboratory support.
Publisher Copyright:
© 2021 John Wiley & Sons Ltd
PY - 2021/8/1
Y1 - 2021/8/1
N2 - Aims: Determining prognosis following poor response to neoadjuvant chemoradiotherapy (nCRT) in oesophageal adenocarcinoma (OAC) remains challenging. An immunosuppressive tumour microenvironment (TME) as well as immune infiltrate density and composition are considered to play a critical role in the immune interaction between host and tumour and can predict therapy response and survival in many cancers, including gastrointestinal malignancies. The aim of this study was to establish the TME characteristics associated with survival following a poor response to nCRT. Methods and results: The prognostic significance of OAC-associated CD3+, CD4+, CD8+, forkhead box protein 3 (FoxP3+) and programmed cell death ligand 1 (PD-L1) expression was studied by immunohistochemistry and quantified by automated image analysis in 123 patients who underwent nCRT and curative resection. Results from good and poor responders were contrasted and immune infiltration was related to disease course in both groups. Subsequently a cohort of 57 patients with a moderate response to nCRT was analysed in a similar fashion. Tumour cell percentage positively correlated to immune infiltration markers. In good and moderate responders, none of the immune infiltrate parameters was associated with survival; in poor responders CD8+ was an independent negative predictor of OS in univariate analysis (P = 0.03) and high CD8+ infiltration was associated with worse OS (15 versus 32 months, P = 0.042). Conclusion: A high CD8+ density is an independent biomarker of poor OS in poor responders to nCRT, but not in good and moderate responders. Our results suggest that patients with a poor response to nCRT but concomitant high CD8+ counts in the resection specimen require adjuvant therapy.
AB - Aims: Determining prognosis following poor response to neoadjuvant chemoradiotherapy (nCRT) in oesophageal adenocarcinoma (OAC) remains challenging. An immunosuppressive tumour microenvironment (TME) as well as immune infiltrate density and composition are considered to play a critical role in the immune interaction between host and tumour and can predict therapy response and survival in many cancers, including gastrointestinal malignancies. The aim of this study was to establish the TME characteristics associated with survival following a poor response to nCRT. Methods and results: The prognostic significance of OAC-associated CD3+, CD4+, CD8+, forkhead box protein 3 (FoxP3+) and programmed cell death ligand 1 (PD-L1) expression was studied by immunohistochemistry and quantified by automated image analysis in 123 patients who underwent nCRT and curative resection. Results from good and poor responders were contrasted and immune infiltration was related to disease course in both groups. Subsequently a cohort of 57 patients with a moderate response to nCRT was analysed in a similar fashion. Tumour cell percentage positively correlated to immune infiltration markers. In good and moderate responders, none of the immune infiltrate parameters was associated with survival; in poor responders CD8+ was an independent negative predictor of OS in univariate analysis (P = 0.03) and high CD8+ infiltration was associated with worse OS (15 versus 32 months, P = 0.042). Conclusion: A high CD8+ density is an independent biomarker of poor OS in poor responders to nCRT, but not in good and moderate responders. Our results suggest that patients with a poor response to nCRT but concomitant high CD8+ counts in the resection specimen require adjuvant therapy.
UR - http://www.scopus.com/inward/record.url?scp=85110170278&partnerID=8YFLogxK
U2 - 10.1111/his.14361
DO - 10.1111/his.14361
M3 - Article
C2 - 33660299
AN - SCOPUS:85110170278
SN - 0309-0167
VL - 79
SP - 238
EP - 251
JO - Histopathology
JF - Histopathology
IS - 2
ER -
