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World J Gastrointest Oncol. Jun 15, 2025; 17(6): 106707
Published online Jun 15, 2025. doi: 10.4251/wjgo.v17.i6.106707
Immune checkpoint inhibitors in the first-line treatment of esophageal squamous cell carcinoma: Minireview for a big shift
Giulia Massaro, Alexandra Paulet, Daniele Lavacchi, Marco Brugia, Daniele Rossini, Elisa Giommoni, Martina Catalano, Serena Pillozzi, Lorenzo Antonuzzo, Giandomenico Roviello
Giulia Massaro, Alexandra Paulet, School of Human Health Sciences, University of Florence, Florence 50134, Tuscany, Italy
Daniele Lavacchi, Oncology Unit, Careggi University Hospital, Florence 50134, Tuscany, Italy
Marco Brugia, Elisa Giommoni, Oncology Unit, Azienda Universitaria Ospedaliera Careggi, Florence 50134, Tuscany, Italy
Daniele Rossini, Serena Pillozzi, Lorenzo Antonuzzo, Department of Experimental and Clinical Medicine, University of Florence, Florence 50134, Tuscany, Italy
Martina Catalano, Giandomenico Roviello, Department of Health Sciences, University of Florence, Florence 50134, Tuscany, Italy
Co-first authors: Giulia Massaro and Alexandra Paulet.
Co-corresponding authors: Martina Catalano and Giandomenico Roviello.
Author contributions: Antonuzzo L and Roviello G contributed to the conceptualization of this study; Rossini D, Pillozzi S, and Roviello G were involved in the methodology; Lavacchi D, Rossini D, and Catalano M participated in the validation; Massaro G and Paulet A contributed to the investigation, resources and, writing the original draft of this manuscript; Massaro G curated data; Brugia M, Giommoni E, and Catalano M contributed to reviewing and editing this manuscript; Pillozzi S and Antonuzzo L contributed to the visualization of this study; Lavacchi D, Rossini D, and Catalano M participated in the supervision. Massaro G and Paulet A are co-first authors and contributed equally to this work. Both authors made significant intellectual contributions, including jointly designing the study, acquiring and analyzing experimental data, and co-writing the manuscript. Their collaborative efforts were integral to the development and completion of the research. Catalano M and Roviello G are co-corresponding authors and contributed equally to the supervision and oversight of this work. Both authors were jointly involved in guiding the research design, interpreting results, and revising the manuscript. Roviello G will serve as the primary corresponding author and will take lead responsibility for all communications with the journal throughout the submission, peer review, and publication process, as well as ensuring all journal administrative requirements are met.
Conflict-of-interest statement: All authors report no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Giandomenico Roviello, MD, PhD, Associate Professor, Department of Health Sciences, University of Florence, Viale Pieraccini, Florence 50134, Tuscany, Italy. giandomenico.roviello@unifi.it
Received: March 5, 2025
Revised: April 9, 2025
Accepted: April 23, 2025
Published online: June 15, 2025
Processing time: 100 Days and 23 Hours
Core Tip

Core Tip: This paper examined the evolving landscape of first-line treatments for esophageal squamous cell carcinoma, highlighting the transformative impact of immune checkpoint inhibitors. While immune checkpoint inhibitors combined with chemotherapy have improved survival, response rates remain inconsistent due to variability in programmed death ligand 1 testing and immune microenvironment changes. We critically analyzed landmark phase 3 trials (KEYNOTE-590, CheckMate 648) and discussed the limitations of current biomarkers. Addressing the urgent need for more precise patient selection and novel therapeutic strategies, this review provided insights into emerging approaches that could enhance long-term survival in esophageal squamous cell carcinoma.