Tumor-Infiltrating Neutrophils after Neoadjuvant Therapy are Associated with Poor Prognosis in Esophageal Cancer

Cabalag, CS; Prall, OWJ; Ciciulla, J; Galea, LA; Thio, N; Jayawardana, M; Leong, TYM; Milne, JV; Fujihara, KM; Chong, L; Hii, MW; Arnau, GM; Neeson, PJ; Phillips, WA; Duong, CP; Clemons, NJ

Author(s): Cabalag, CS; Prall, OWJ; Ciciulla, J; Galea, LA; Thio, N; Jayawardana, M; Leong, TYM; Milne, JV; Fujihara, KM; Chong, L; Hii, MW; Arnau, GM; Neeson, PJ; Phillips, WA; Duong, CP; Clemons, NJ;
Details: Publication Year 2023-03,Volume 30,Issue #3,Page 1614-1625
Journal Title: Annals of Surgical Oncology
Publication Type: Research article
Abstract: BACKGROUND: In esophageal cancer (EC), there is a paucity of knowledge regarding the interplay between the tumor immune microenvironment and response to neoadjuvant treatment and, therefore, which factors may influence outcomes. Thus, our goal was to investigate the changes in the immune microenvironment with neoadjuvant treatment in EC by assessing the expression of immune related genes and their association with prognosis. METHODS: We examined the transcriptome of paired pre- and post-neoadjuvant treated EC specimens. Based on these findings, we validated the presence of tumor-infiltrating neutrophils using CD15(+) immunohistochemistry in a discovery cohort of patients with residual pathologic disease. We developed a nomogram as a predictor of progression-free survival (PFS) incorporating the variables CD15(+) cell count, tumor regression grade, and tumor grade. RESULTS: After neoadjuvant treatment, there was an increase in genes related to myeloid cell differentiation and a poor prognosis associated with high neutrophil (CD15(+)) counts. Our nomogram incorporating CD15(+) cell count was predictive of PFS with a C-index of 0.80 (95% confidence interval [CI] 0.68-0.9) and a concordance probability estimate (CPE) of 0.77 (95% CI 0.69-0.86), which indicates high prognostic ability. The C-index and CPE of the validation cohort were 0.81 (95% CI 0.69-0.91) and 0.78 (95% CI 0.7-0.86), respectively. CONCLUSIONS: Our nomogram incorporating CD15(+) cell count can potentially be used to identify patients at high risk of recurrent disease and thus stratify patients who will benefit most from adjuvant treatment.
Publisher: Springer Nature
Keywords: Humans; *Neutrophils/pathology; Neoadjuvant Therapy; *Esophageal Neoplasms/pathology; Prognosis; Nomograms; Tumor Microenvironment
Department(s): Laboratory Research; Surgical Oncology; Pathology
PubMed ID: 36183015
Publisher's Version: https://doi.org/10.1245/s10434-022-12562-5
Open Access at Publisher's Site: https://doi.org/10.1245/s10434-022-12562-5
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2023-06-22 07:56:51

Last Modified: 2023-06-22 07:57:28