• Toshiki Noma, Tomoki Makino, Kenji Ohshima, Keijiro Sugimura, Hiroshi Miyata, Keiichiro Honma, Kotaro Yamashita, Takuro Saito, Koji Tanaka, Kazuyoshi Yamamoto, Tsuyoshi Takahashi, Yukinori Kurokawa, Makoto Yamasaki, Kiyokazu Nakajima, Eiichi Morii, Hidetoshi Eguchi, and Yuichiro Doki.
• Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita City, Osaka, Japan.
• Ann. Surg. 2023 Mar 1; 277 (3): e528e537e528-e537.

ObjectivesTumor-infiltrating lymphocytes (TILs) have long been recognized as playing an important role in tumor immune microenvironment. Lately, the Immunoscore (IS) has been proposed as a new method of quantifying the number of TILs in association with patient survival in several cancer types.MethodsIn 300 preoperatively untreated esophageal cancer (EC) patients who underwent curative resection at two different institutes, immunohistochemical staining using CD3 and CD8 antibodies was performed to evaluate IS, as objectively scored by auto-counted TILs in the tumor core and invasive margin. In addition, in pre-neoadjuvant chemotherapy (pre-NAC) endoscopic biopsies of a different cohort of 146 EC patients who received NAC, CD3, and CD8 were immunostained to evaluate TIL density.ResultsIn all cases, the IS-high (score 3-4) group tended to have better survival [5-year overall survival (OS) of the IS-high vs low group: 77.6 vs 65.8%, P = 0.0722] than the IS-low (score 1-2) group. This trend was more remarkable in cStage II-IV patients (70.2 vs 54.5%, P = 0.0208) and multivariate analysis of OS further identified IS (hazard ratio 2.07, P = 0.0043) to be an independent prognostic variable. In preNAC biopsies, NAC-responders had higher densities than non-responders of both CD3 + ( P = 0.0106) and CD8 + cells ( P = 0.0729) and, particularly CD3 + cell density was found to be an independent prognostic factor (hazard ratio 1.75, P = 0.0169).ConclusionsThe IS signature in surgical specimens and TIL density in preNAC- biopsies could be predictive markers of clinical outcomes in EC patients.Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

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