2398 Prognostic significance of tumour-infiltrating immune cells and PD-L1 expression in oesophageal squamous cell carcinoma in Chinese patients

13 Background: Programmed death-1 receptor (PD-1) and its ligand (PD-L1) play an integral role in the immune response against cancer. This study investigated the prognostic significance of PD-L1 expression and tumor-infiltrating immune cells (TILs) in tumor microenvironment in Chinese patients with esophageal squamous cell carcinoma (ESCC). Methods: A total of 428 archival formalin-fixed, paraffin-embedded (FFPE) ESCC samples were collected between 2004 and 2014 from treatment naïve patients with ESCC after surgery or by diagnostic endoscopic biopsy. Expression of PD-L1 was assessed by IHC. The degree of TILs infiltration was evaluated by examining the H&E-stained specimens. Associations of PD-L1 expression and TILs with clinicopathological features were evaluated by non-zero correlation test. Survival distribution was compared by Kaplan-Meier and a log-rank test. The median follow-up time was 34.4 months(0.3-147.1 m). Changes of PD-L1 expression between paired tumor samples, which were collected before and after chemotherapy (2 cycles and 4 cycles or more), were also evaluated. Results: In the entire cohort, 79.7% (341/428) of specimens were PD-L1+ (defined as having ≥ 1% of tumor cell membranes showing ≥ 1+ intensity). In the intent-to-treat group (patients received curative esophagectomy or definitive chemoradiation therapy), PD-L1 positivity was associated with a significantly poorer DFS and OS. Neither PFS nor OS in palliative chemotherapy group presented a significant difference corresponding to PD-L1 expression. Furthermore, PD-L1 expression was positively associated with TIL density. Changes in PD-L1 expression was examined in 17 paired tumor tissues collected before and after treatments. Results showed that an increase in PD-L1 expression was associated with disease progression, a decrease in PD-L1 expression was associated with satisfactory chemotherapy treatment response. Conclusions: PositivePD-L1 expression was associated with a significantly worse prognosis in ESCC. These observations suggest that PD-L1 may play a critical role in ESCC cancer progression and provide a rationale for developing PD-L1 inhibitors for treatment of a subset of ESCC patients.

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Prognostic significance of tumor-infiltrating immune cells and PD-L1 expression in esophageal squamous cell carcinoma

Oncotarget ◽

10.18632/oncotarget.15621 ◽

2017 ◽

Vol 8 (18) ◽

pp. 30175-30189 ◽

Cited By ~ 35

Author(s):

Yubo Jiang ◽

Anthony W.I. Lo ◽

Angela Wong ◽

Wenfeng Chen ◽

Yan Wang ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Immune Cells ◽

Prognostic Significance

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The presence of tumour-infiltrating lymphocytes (TILs) and the ratios between different subsets serve as prognostic factors in advanced hypopharyngeal squamous cell carcinoma

10.21203/rs.3.rs-22036/v2 ◽

2020 ◽

Author(s):

Jie Wang ◽

Shu Tian ◽

Ji Sun ◽

Jiahao Zhang ◽

Lan Lin ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Immune Cells ◽

Univariate Analysis ◽

Prognostic Significance ◽

Free Survival ◽

Hypopharyngeal Squamous Cell Carcinoma ◽

Tumour Infiltrating Lymphocytes ◽

Infiltrating Lymphocytes

Abstract Background: Cancer cells induce the infiltration of various immune cells that are located or distributed in different sites and play multiple roles, which have recently been proposed to predict clinical outcomes. We therefore studied the prognostic significance of the presence of tumour-infiltrating lymphocytes (TILs) and the ratios between different types of immune cells in hypopharyngeal squamous cell carcinoma (HPSCC). Methods: We retrospectively analysed 132 consecutive patients diagnosed with advanced HPSCC in 2013-2017. Tumoural parenchyma was immunohistochemically counted manually for the number of CD8, CD4 and Foxp3 cells. The ratios of CD8/Foxp3 and CD8/CD4 ratios were calculated for each specimen and analyzed with respect to patient clinicopathological variables and prognosis. Results: HPSCC patients with high levels of TILs showed evident correlations with well differentiated tumors (P < 0.05). Moreover, Foxp3+ TIL is also associated with overall staging group and T category (P =0.048 and P= 0.046, respectively). Kaplan-Meier analysis showed that high CD8 and FoxP3 infiltration correlated with favourable overall survival (OS, P = 0.019 and P = 0.001), disease-free survival (DFS, P = 0.045 and P = 0.028) and distant metastasis-free survival (DMFS, P = 0.034 and P = 0.009), respectively, but only Foxp3 displayed prognostic significance for DMFS in multivariate analysis (MVA). In the lymphocyte ratio analysis, CD8/Foxp3 appeared to play a pivotal role, and patients with a high CD8/Foxp3 ratio had a superior 3-year DFS and DMFS compared with those a low CD8/Foxp3 ratio in both univariate analysis (UVA) and MVA (P = 0.015 and P=0.011). A high CD8/CD4 ratio was associated with better DFS and local relapse-free survival (LRFS) in UVA, and was an independent prognostic factor for improved LRFS in MVA (P = 0.040).Conclusion: Although high TILs levels were determined to be prognostically significant in advanced HPSCC, the ratios of these subsets may be more informative. Particularly, a higher ratio of CD8/Foxp3 accurately predicts prognosis for improved DFS and DMFS, and an increased CD8/CD4 ratio is an independent predictor for favourable LRFS.

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Expressions of melanoma-associated antigen A1 as a prognostic factor in Chinese patients with resectable oesophageal squamous cell carcinoma

Interactive CardioVascular and Thoracic Surgery ◽

10.1093/icvts/ivz141 ◽

2019 ◽

Vol 29 (4) ◽

pp. 510-516 ◽

Cited By ~ 1

Author(s):

Yue Yu ◽

Chenjun Huang ◽

Zhihua Li ◽

Fei Zhao ◽

Yue Zhou ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Survival Rate ◽

Prognostic Factor ◽

Cell Carcinoma ◽

Squamous Cell ◽

Independent Predictor ◽

Chinese Patients ◽

Oesophageal Squamous Cell Carcinoma ◽

Oesophageal Mucosa ◽

History Of

AbstractOBJECTIVESMelanoma-associated antigen A1 (MAGEA1) is a potential target for immunotherapy and has been associated with poor survival rate in several cancers. However, little is known about the prognostic predictive value of MAGEA1 in oesophageal squamous cell carcinoma (OSCC). This study aims to determine whether the expression of MAGEA1 is an independent predictor of survival in patients with resectable OSCC.METHODSA retrospective analysis was performed on a large cohort of 197 patients with OSCC who underwent radical surgical treatment in the Department of Thoracic Surgery between January 2006 and December 2012. The expression of MAGEA1 in OSCC and matched normal oesophageal mucosa specimens from these patients was detected by immunohistochemistry with tissue microarray technology.RESULTSThe MAGEA1 protein was expressed in the cytoplasm and nucleus of tumour cells. The positive expression rate of MAGEA1 was significantly higher in OSCC tissue than in normal oesophageal mucosa (73.6% vs 5.6%, P < 0.001). MAGEA1 expression had no correlations with sex, age, history of smoking, alcohol consumption, family history of upper gastrointestinal cancer, T stage, lymph node metastasis, grade/location of the tumour or TNM stage (all at P > 0.05). Compared with those with negative MAGEA1 expression, patients with positive MAGEA1 expression were associated with a reduced overall survival rate (5-year survival rate: 53.8% vs 37.2%; P = 0.018). The multivariable analysis revealed that MAGEA1 expression is an independent predictor of prognosis (P = 0.007, hazard ratio 1.85, 95% confidence interval 1.19–2.89).CONCLUSIONSThe expression of MAGEA1 is abundant in Chinese patients with OSCC and is related to a worse clinical outcome. MAGEA1 may be a useful prognostic factor in patients with resectable OSCC.

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Prognostic significance of tumor infiltrating immune cells in oral squamous cell carcinoma

BMC Cancer ◽

10.1186/s12885-017-3317-2 ◽

2017 ◽

Vol 17 (1) ◽

Cited By ~ 46

Author(s):

Juan Fang ◽

Xiaoxu Li ◽

Da Ma ◽

Xiangqi Liu ◽

Yichen Chen ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Immune Cells ◽

Prognostic Significance

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T‑cell immunoglobulin and mucin domain‑containing protein‑3 and galectin‑9 protein expression: Potential prognostic significance in esophageal squamous cell carcinoma for Chinese patients

Oncology Letters ◽

10.3892/ol.2017.7188 ◽

2017 ◽

Author(s):

Nan Hou ◽

Jie Ma ◽

Wei Li ◽

Lingdi Zhao ◽

Quanli Gao ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

T Cell ◽

Esophageal Squamous Cell Carcinoma ◽

Protein Expression ◽

Cell Carcinoma ◽

Squamous Cell ◽

Prognostic Significance ◽

Chinese Patients ◽

Expression Potential

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Abstract LB-219: Interleukin-8 promotes generation of M2 macrophages and arginase-producing granulocytes: Prognostic significance of interleukin-8 and infiltration of immune cells positive for CD163 and CD66b in tumor tissues in patients with oral squamous cell carcinoma

10.1158/1538-7445.am2015-lb-219 ◽

2015 ◽

Author(s):

Masato Okamoto ◽

Yohei Fujita ◽

Hiroyuki Goda ◽

Koh-ichi Nakashiro ◽

Hiroyuki Hamakawa

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Immune Cells ◽

Prognostic Significance ◽

Interleukin 8 ◽

M2 Macrophages ◽

Tumor Tissues

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Relationship between the immune microenvironment of different locations in a primary tumour and clinical outcomes of oesophageal squamous cell carcinoma

British Journal of Cancer ◽

10.1038/s41416-019-0622-3 ◽

2019 ◽

Vol 122 (3) ◽

pp. 413-420 ◽

Cited By ~ 2

Author(s):

Ken Hatogai ◽

Satoshi Fujii ◽

Shigehisa Kitano ◽

Takashi Kojima ◽

Hiroyuki Daiko ◽

...

Keyword(s):

Overall Survival ◽

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Immune Cells ◽

Immune Status ◽

Primary Tumour ◽

Oesophageal Squamous Cell Carcinoma ◽

Invasive Front ◽

Immune Microenvironment

Abstract Background Tumour microenvironments can differ according to intratumoural locations. We investigated the immune status at different locations in primary tumours and its clinical significance in oesophageal squamous cell carcinoma (ESCC). Methods The number of CD8+ tumour-infiltrating immune cells (TIICs) and PD-1+ TIICs, and PD-L1 expression on tumour cells (PD-L1TC) were immunohistochemically examined in the surface (Surf), centre (Cent) and invasive front (Inv) of tumours surgically resected from 192 patients with ESCC. Results The PD-L1+ rate was lower in Inv than in Cent (12.0% vs. 18.2%, P = 0.012), although the numbers of CD8+ TIICs and PD-1+ TIICs were comparable among intratumoural locations. High numbers of CD8+ and PD-1+ TIICs and positive PD-L1TC were related to better overall survival (OS) only in Surf and Cent (CD8: P = 0.012 in Surf, 0.018 in Cent, and 0.165 in Inv; PD-1: P = 0.028 in Surf, 0.021 in Cent, and 0.208 in Inv; and PD-L1: 0.044 in Surf, 0.026 in Cent, and 0.718 in Inv). Positive PD-L1TC in Surf and/or Cent but not in Inv demonstrated a strong tendency toward better OS (P = 0.053). Conclusions Immune microenvironments according to the intratumoural location have different effects on the survival of patients with ESCC.

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