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Despite the promising outcomes of immune checkpoint inhibitors (ICIs), resistance to ICI presents a new challenge. Therefore, selecting patients for specific ICI applications is crucial for maximizing therapeutic efficacy. Herein, we curated 69 human esophageal squamous cell cancer (ESCC) patients' tumor microenvironment (TME) single-cell transcriptomic datasets to subtype ESCC. Integrative analyses of the cellular network and transcriptional signatures of T cells and myeloid cells define distinct ESCC subtypes characterized by T cell exhaustion, and interleukin (IL) and interferon (IFN) signaling. Furthermore, this approach classifies ESCC patients into ICI responders and non-responders, as validated by whole tumor transcriptomes and liquid biopsy-based single-cell transcriptomes of anti-PD-1 ICI responders and non-responders. Our study stratifies ESCC patients based on TME transcriptional network, providing novel insights into tumor niche remodeling and potentially predicting ICI responses in ESCC patients.
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http://dx.doi.org/10.1016/j.isci.2024.109795 | DOI Listing |
Esophagus
September 2025
Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, Japan.
Background: The cluster of differentiation 47 (CD47)-signal regulatory protein alpha (SIRPα) axis is a key regulator of innate immune surveillance, facilitating the neoplastic evasion of macrophage-mediated phagocytosis. Although this pathway has been implicated in tumor immune escape in multiple malignancies, its clinical and prognostic significance in esophageal squamous cell carcinoma (ESCC) remain to be fully elucidated.
Methods: We retrospectively analyzed 100 patients who underwent esophagectomy for resectable ESCC.
Cancer Med
September 2025
Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
Background: Esophageal squamous cell carcinoma (ESCC) represents an aggressive cancer type associated with poor prognosis, often treated with neoadjuvant chemotherapy (NAC) using cisplatin-based regimens. However, cisplatin resistance limits therapeutic efficacy, necessitating a deeper understanding of resistance mechanisms. L-type amino acid transporter 1 (LAT1) plays a crucial role in amino acid uptake and is linked to cancer cell survival through activation of the mammalian target of rapamycin (mTOR) pathway.
View Article and Find Full Text PDFAnn Gastroenterol Surg
September 2025
Division of Gastrointestinal Surgery, Department of Surgery Jikei University School of Medicine Tokyo Japan.
Background: Our previous study suggested that low bone mineral density (BMD), known as osteopenia, was a poor prognostic factor in patients who underwent esophagectomy for esophageal cancer (EC).Meanwhile, the association between BMD reduction during neoadjuvant chemotherapy (NAC) and the worse prognosis remains unknown, although esophagectomy after NAC is the first option for the treatment of advanced esophageal squamous cell carcinoma (ESCC). Therefore, this study intended to investigate the prognostic impact of BMD reduction during NAC.
View Article and Find Full Text PDFAnn Gastroenterol Surg
September 2025
Department of Gastrointestinal Surgery, Graduate School of Medicine The University of Tokyo Tokyo Japan.
Background: This study aimed to investigate survival outcomes, the efficacy of lymph node (LN) dissection, and recurrence patterns in patients who underwent salvage surgery (SALV) for esophageal squamous cell carcinoma (ESCC) after definitive chemoradiotherapy (dCRT).
Methods: We retrospectively reviewed 69 patients with clinical stage I-IV thoracic ESCC who underwent SALV. Recurrence patterns and the distribution of LN metastases were analyzed according to the primary tumor location.
Ann Gastroenterol Surg
September 2025
We reviewed the current status and perspectives on salvage esophagectomy for initially unresectable locally advanced esophageal squamous cell carcinoma (ESCC) in the era of minimally invasive surgery and immunotherapy. Although the standard treatment for these patients is definitive chemoradiotherapy (CRT), the complete response rate to CRT alone remains unsatisfactory. Salvage esophagectomy, which is defined as surgery for residual or recurrent lesions after definitive CRT, is considered a curative treatment in clinical practice.
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