Tumour infiltrating lymphocytes correlate with improved survival in patients with esophageal squamous cell carcinoma

Abstract

We undertook a study of tumour infiltrating lymphocytes (TILs) in a large and relatively homogeneous group of patients with completely resected esophageal squamous cell carcinoma (ESCC). Hematoxylin and eosin–stained sections of 235 ESCC tumours were evaluated for density of TILs in intratumoural (iTIL) and stromal compartments (sTIL). Foxp3+, CD4+, and CD8+ T cells in tumoural and stromal areas were evaluated by immunohistochemistry. Of the 235 tumours, high sTIL (>10%), and iTIL (>10%) were observed in 101 (43.0%) and 98 (41.7%), respectively. The median follow-up period was 36.0 months (95% CI 29.929–42.071). Univariate analysis revealed that sTIL (>10%), iTIL (>20%), vessels involvement, lymph node metastasis, and clinical stage were significantly associated with postoperative outcome. In multivariate analysis, high sTIL (HR: 0.664, P = 0.019 for Disease free survival; HR: 0.608, P = 0.005 for Overall survival) was identified as independent better prognostic factor. Further analysis, sTIL was identified as independently prognostic factor in Stage III-IVa disease, which was not found in Stage I-II disease. Our study demonstrated that sTIL was associated with better ESCC patients’ survival, especially in Stage III-IVa disease. Assessment of sTIL could be useful to discriminate biological behavior for ESCC patients.

Nomogram for prediction of lymph node metastasis in patients with superficial esophageal squamous cell carcinoma

“…b) . Tumor infiltrating lymphocytes (TILs) were defined as lymphocytes that infiltrated tumor nests and/or abutted tumor cells . The grade of TIL was reported using a four‐tier system according to the grading for cutaneous malignant melanoma .…”

PD‐1 and PD‐L1 expression in HNSCC primary cancer and related lymph node metastasis – impact on clinical outcome

“…PD-1 expression in lymphocytes was evaluated intratumourally, based on the number of positive TILs counted in three high-power fields (HPF) (400-fold magnification) of highest density. Stratification was made for negative expression (0-5), weak (6)(7)(8)(9)(10)(11)(12)(13)(14)(15), moderate (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) or strong (>30) infiltration patterns.…”

“…The prognostic significance of TILs has been evaluated in several malignancies, including breast cancer, non-small-cell lung cancer and oesophageal squamous cell carcinoma, revealing better clinical outcome when high levels of TILs are present. [6][7][8] In HNSCC, high levels of TILs are associated with favourable patient survival. [9][10][11][12] However, studies focusing on the prognostic relevance of PD-1-expressing TILs in HNSCC are sparse.…”

Immune signature profiling identified predictive and prognostic factors for esophageal squamous cell carcinoma

“…16 Immune disorders in tumor is regarded as a promoting factor during tumorigenesis and development. 17,18 Immune responses stimulated by tumor antigens, which are supposed to eradicate tumor cells, are even subjugated to provide proper microenvironment for tumor growth. 17 With intensive efforts made to elucidate the interactions between the tumor and the immune system, [19][20][21] remarkable success has been achieved in cancer immunotherapy in treating advanced tumors, but only applicable to a substantial fraction of patients while others either are not suitable or failed to respond.…”

“…21 Considering the poor outcome after standard treatment and few targeted therapeutics in ESCC, immunotherapy, a promising additional approach, is currently under intensive investigation. Meanwhile, several immune-related parameters, mainly tumor infiltrating lymphocytes, have been reported for predicting ESCC patient prognosis, 18,22,23 further suggesting distinct immune status has profound influence on outcome of ESCC patients. Therefore, systematically investigation of the immune phenotype within the ESCC microenvironment is great needed to better understand the complex antitumor response and guide effective immunotherapies in ESCC.…”