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. 2023 Dec 5;23(1):1193.
doi: 10.1186/s12885-023-11684-7.

Prognostic value of Hematoxylin and eosin staining tumor-infiltrating lymphocytes (H&E-TILs) in patients with esophageal squamous cell carcinoma treated with chemoradiotherapy

Jifang Zheng #  1 , Hejun Zhang #  2 , Siya Li #  1 , Zhaoxin Kang  1   3 , Fei Zheng  1 , Qiwei Yao  1 , Xueqing Zhang  1 , Ziyi Wu  1 , Jiezhong Wang  1 , Weimin Fang  4 , Jiancheng Li  1 , Gang Chen  2 , Yuangui Chen  5 , Mingqiu Chen  6
Affiliations

Prognostic value of Hematoxylin and eosin staining tumor-infiltrating lymphocytes (H&E-TILs) in patients with esophageal squamous cell carcinoma treated with chemoradiotherapy

Jifang Zheng et al. BMC Cancer. .

Abstract

Background: Tumor-infiltrating lymphocytes (TILs) by routine hematoxylin and eosin staining (H&E-TILs) are a robust prognostic biomarker in various cancers. However, the role of H&E-TILs in esophageal squamous cell carcinoma (ESCC) treated with concurrent chemoradiotherapy (CCRT) has not been reported. The purpose of this study was to assess the prognostic value of H&E-TILs in ESCC treated with CCRT.

Methods: The clinical data of 160 patients with ESCC treated with CCRT in our center between Jan. 2014 and Dec. 2021 were collected and retrospectively reviewed, and propensity score matching (PSM) analyses were performed. The H&E-TILs sections before CCRT were reassessed by two experienced pathologists independently. The H&E-TILs sections were classified into a positive group (+, > 10%) and a negative group (-, ≤ 10%) using 10% as the cutoff. The effects of H&E-TILs on overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS) were explored using the Kaplan‒Meier method, and the log-rank test was used to test the differences. Multivariable analysis was performed using the Cox proportion hazards model.

Results: The short-term response to CCRT and the OS (P < 0.001), DMFS (P = 0.001), and LRFS (P < 0.001) rates were significantly different between the H&E-TILs (+) and H&E-TILs (-) groups. Subgroup analysis showed that H&E-TILs(+) with CR + PR group had a longer survival than H&E-TILs(-) with CR + PR, H&E-TILs(+) with SD + PD and H&E-TILs(-) with SD + PD group, respectively(P < 0.001). Furthermore, based on TCGA data, patients in the high TILs group had a better prognosis than those in the low TILs group. Multivariate analyses indicated that H&E-TILs and the short-term response to CCRT were the only two independent factors affecting OS, PFS, DMFS, and LRFS simultaneously, and H&E-TILs expression was associated with an even better prognosis for those patients with CR + PR.

Conclusions: H&E-TILs may be an effective and beneficial prognostic biomarker for ESCC patients treated with CCRT. Patients with H&E-TILs (+) with PR + CR would achieve excellent survival. Further prospective studies are required to validate the conclusions.

Keywords: Chemoradiotherapy; ESCC; Prognosis; TILs.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Percentage level of TILs on H&E stained sections. The ratio of infiltration: a 0%, b 0–10%, c 11–20%, d 21–30% e31-50%, f > 50% (200x magnification). TILs Tumor-infiltrating lymphocytes, H&E Hematoxylin and eosin
Fig. 2
Fig. 2
OS between the low TILs and the high TILs group in the whole cohort from the TCGA database. The high TILs group had a better prognosis of OS. OS Overall survival, TILs Tumor-infiltrating lymphocytes, TCGA The Cancer Genome Atlas
Fig. 3
Fig. 3
Association between TILs (+) and OS, PFS, DMFS, and LRFS in 160 patients. TILs (+) are beneficial for OS, PFS, DMFS, and LRFS among ESCC patients. a OS between TILs (+) and TILs (-) in the whole cohort; b PFS between TILs (+) and TILs (-) in the whole cohort; c DMFS between TILs (+) and TILs (-) in the whole cohort; d LRFS between TILs (+) and TILs (-) in the whole cohort. TILs Tumor-infiltrating lymphocytes, OS Overall Survival, PFS Progression-free Survival, DMFS Distant Metastasis-free Survival, LRFS Locoregional Recurrence-free survival
Fig. 4
Fig. 4
Association between TILs (+) and OS, PFS, DMFS, and LRFS in 121 patients after PSM. TILs (+) are also beneficial for OS, PFS, DMFS, and LRFS among ESCC patients. a OS between TILs (+) and TILs (-) in the whole cohort; (b) PFS between TILs (+) and TILs (-) in the whole cohort; (c) DMFS between TILs (+) and TILs (-) in the whole cohort; (d) LRFS between TILs (+) and TILs (-) in the whole cohort. TILs Tumor-infiltrating lymphocytes, PSM Propensity score matching, OS Overall Survival, PFS Progression-free Survival, DMFS Distant Metastasis-free Survival, LRFS Locoregional Recurrence-free survival
Fig. 5
Fig. 5
OS of patients according to the different combination of the short-term response and TIL. The TILs (+/-) CR + PR group had significantly longer survival than that in the TILs (+/-) PD + SD group, respectively. Further, TILs (+) CR + PR group had better OS than the TILs (-) CR + PR group, and the difference were significant (p < 0.05). OS Overall survival, TILs Tumor-infiltrating lymphocytes, CR Complete response, PR Partial response, SD Stable disease, PD Progressive disease
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