Dataset Information

Association of Sialic Acid-Binding Immunoglobulin-Like Lectin 15 With Phenotypes in Esophageal Squamous Cell Carcinoma in the Setting of Neoadjuvant Chemoradiotherapy.

ABSTRACT:

Importance

Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) is a novel immune checkpoint molecule that is highly homologous to programmed cell death ligand 1 (PD-L1), but information remains limited about its role in esophageal squamous cell carcinoma (ESCC).

Objective

To explore the expression pattern and association of Siglec-15 with outcomes among patients with ESCC who received neoadjuvant chemoradiotherapy (CRT).

Design, setting, and participants

This retrospective cohort study was conducted at an academic institution in China. Participants included patients with ESCC who underwent neoadjuvant CRT and esophagectomy between June 2002 and December 2018. Multiplexed immunofluorescence staining was used to evaluate the expression of Siglec-15 and PD-L1 in tumor cells (TCs) or tumor-associated macrophages based on pre-CRT biopsies. Different immune phenotypes have been proposed and further validated in an independent cohort. Data analysis was conducted from January to May 2021.

Exposures

Siglec-15 or PD-L1 positivity vs negativity.

Main outcomes and measures

Pathologic complete response (pCR), overall survival (OS), and recurrence-free survival (RFS).

Results

Of 130 participants (median [range] age, 56 [42-73] years; 108 [83.1%] male participants) in the primary cohort, 58 patients (44.6%) achieved a pCR after neoadjuvant CRT. Siglec-15 and PD-L1 were detected in both TCs and macrophages. The percentage of Siglec-15-positive macrophages was notably higher than that of Siglec-15-positive TCs (median [IQR]: 34.4% [12.7%-64.3%] vs 4.8% [0.7%-25.6%]; P < .001). TC-Siglec-15 expression was significantly and positively associated with macrophage-Siglec-15 expression (r = 0.78; P < .001). Siglec-15 positivity was significantly associated with a higher rate of pCR (37 of 70 [52.9%] vs 21 of 60 [35.0%]; P = .04), more favorable OS (hazard ratio [HR], 0.46; 95% CI, 0.25-0.85; P = .01), and RFS (HR, 0.48; 95% CI, 0.26-0.88; P = .02). However, PD-L1 positivity in TCs was negatively associated with survival. Stratification analysis further revealed that patients with combined Siglec-15 positivity and PD-L1 negativity had better survival than those with other phenotypes. Major findings were reproducible in a validation cohort with 55 patients.

Conclusions and relevance

In this cohort study of patients with ESCC receiving neoadjuvant CRT, Siglec-15 positivity was associated with a better pathological response and more favorable survival. Siglec-15 could serve as a novel biomarker to identify potential candidates that may benefit from immunotherapy combined with CRT.

SUBMITTER: Zhou S

PROVIDER: S-EPMC9856737 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Publications

Association of Sialic Acid-Binding Immunoglobulin-Like Lectin 15 With Phenotypes in Esophageal Squamous Cell Carcinoma in the Setting of Neoadjuvant Chemoradiotherapy.

Zhou Sha S Wang Yuting Y Zhang Rui R Zeng Weian W Liu Shiliang S Liu Songran S Liu Mengzhong M Yang Hong H Xi Mian M

JAMA network open 20230103 1

<h4>Importance</h4>Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) is a novel immune checkpoint molecule that is highly homologous to programmed cell death ligand 1 (PD-L1), but information remains limited about its role in esophageal squamous cell carcinoma (ESCC).<h4>Objective</h4>To explore the expression pattern and association of Siglec-15 with outcomes among patients with ESCC who received neoadjuvant chemoradiotherapy (CRT).<h4>Design, setting, and participants</h4>This retr ...[more]

PMID: 36648946

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Project description:ImportanceThe association of neoadjuvant chemoimmunotherapy (NCIT) vs chemoradiotherapy (NCRT) with tumor downstaging and survival in locally advanced esophageal squamous cell carcinoma (ESCC) remains unclear because of limited evidence.ObjectiveTo compare the associations of NCIT and NCRT with tumor regression and long-term survival in patients with locally advanced ESCC.Design, setting, and participantsIn this comparative effectiveness research study, from January 2016 to March 2023, patients with locally advanced ESCC who underwent esophagectomy following NCRT or NCIT were identified from a prospective database of 8 high-volume esophageal surgery centers in China. Follow-up began on the date of surgery and continued until the last recorded contact or March 2024, whichever occurred first. Data were analyzed between April and September 2024.Main outcomes and measuresThe primary end points were 2-year overall survival (OS) and disease-free survival (DFS). Secondary end points included major pathologic response (MPR) and pathologic complete response (pCR). Cox proportional hazard regression analysis was used to investigate the risk factors for OS and DFS.ResultsThe study included 1428 patients (median [IQR] age, 63 [57-68] years; 1184 men [82.9%]), with 704 patients in the NCRT group and 724 patients in the NCIT group. After propensity score matching, there were 532 patients in each group. The 2-year OS (81.3% vs 71.3%; hazard ratio, 1.57; 95% CI, 1.26-1.96; P < .001) and DFS (73.9% vs 63.4%; hazard ratio, 1.37; 95% CI, 1.11-1.69; P < .001) rates were significantly higher in NCIT group than in the NCRT group. The NCRT group had a higher MPR rate than that of the NCIT group (71.8% vs 61.5%), whereas the pCR rates were similar (25.9% vs 22.9%). Multivariable Cox analysis demonstrated that NCIT and MPR were independently associated with both OS and DFS. The NCIT group exhibited a lower overall recurrence rate (126 patients [23.7%] vs 190 patients [35.7%]) and distant metastasis rate (72 patients [13.5%] vs 133 patients [25.0%]), although locoregional metastasis rates were similar (98 patients [18.4%] vs 111 patients [20.9%]). Better OS and DFS were obtained for the NCIT group than for the NCRT group, regardless of whether adjuvant immunotherapy was given.Conclusions and relevanceCompared with NCRT, patients with locally advanced ESCC receiving NCIT had better 2-year OS and DFS. The decrease in distant metastasis may be the main reason, but further prospective randomized clinical trials are needed to verify this finding.

Project description:BackgroundProgrammed death 1 (PD-1) inhibitor demonstrated durable antitumor activity in advanced esophageal squamous cell carcinoma (ESCC), but the clinical benefit of perioperative immunotherapy in ESCC remains unclear. This study evaluated the efficacy and safety of neoadjuvant chemoradiotherapy (nCRT) combined with the PD-1 inhibitor toripalimab in patients with resectable ESCC.MethodsFrom July 2020 to July 2022, 21 patients with histopathologically confirmed thoracic ESCC and clinical staged as cT1-4aN1-2M0/cT3-4aN0M0 were enrolled. Eligible patients received radiotherapy (23 fractions of 1.8 Gy, 5 fractions a week) with concurrent chemotherapy of paclitaxel/cisplatin (paclitaxel 45 mg/m2 and cisplatin 25 mg/m2) on days 1, 8, 15, 22, 29 and two cycles of toripalimab 240 mg every 3 weeks after nCRT for neoadjuvant therapy before surgery, four cycles of toripalimab 240 mg every 3 weeks for adjuvant therapy after surgery. The primary endpoint was the major pathological response (MPR) rate. The secondary endpoints were safety and survival outcomes.ResultsA total of 21 patients were included, of whom 20 patients underwent surgery, 1 patient refused surgery and another patient was confirmed adenocarcinoma after surgery. The MPR and pathological complete response (pCR) rates were 78.9% (15/19) and 47.4% (9/19) for surgery ESCC patients. 21 patients (100.0%) had any-grade treatment-related adverse events, with the most common being lymphopenia (100.0%), leukopenia (85.7%), neutropenia (52.4%). 14 patients (66.7%) had adverse events of grade 3 with the most common being lymphopenia (66.7%). The maximum standardized uptake value and total lesion glycolysis of positron emission tomography/CT after neoadjuvant therapy well predicted the pathological response. The peripheral CD4+%, CD3+HLA-DR+/CD3+%, CD8+HLA-DR+/CD8+%, and IL-6 were significant differences between pCR and non-pCR groups at different times during neoadjuvant therapy. Three patients had tumor relapse and patients with MPR have longer disease-free survival than non-MPR patients.ConclusionsnCRT combined with perioperative toripalimab is effective and safe for locally advanced resectable ESCC. Long-term survival outcomes remain to be determined.Trial registration numberNCT04437212.

Dataset Information

Association of Sialic Acid-Binding Immunoglobulin-Like Lectin 15 With Phenotypes in Esophageal Squamous Cell Carcinoma in the Setting of Neoadjuvant Chemoradiotherapy.

Importance

Objective

Design, setting, and participants

Exposures

Main outcomes and measures

Results

Conclusions and relevance

Publications

Association of Sialic Acid-Binding Immunoglobulin-Like Lectin 15 With Phenotypes in Esophageal Squamous Cell Carcinoma in the Setting of Neoadjuvant Chemoradiotherapy.

Similar Datasets

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